vitamin-b-12 and Anemia--Megaloblastic

Vitamin B12, or cobalamin, belongs to the group of water-soluble vitamins and is ingested through food of animal origin such as eggs, milk, red meat and poultry, fish, and shellfish. Its clinical indication is the treatment of hypovitaminosis B12 administered orally or intramuscularly in the form of hydroxocobalamin. Hypovitaminosis B12 is mainly caused by deficient dietary intake (individuals with malnutrition, vegetarians or vegans, older adults, pregnant people, individuals with alcohol use disorder); when intestinal absorption is reduced (atrophic gastritis, malabsorption syndrome, gastrointestinal surgery); and for causes associated with the intake of drugs (antacids, metformin). Hypervitaminosis B12 has been associated with renal failure; liver diseases such as cirrhosis and acute-phase hepatitis; alcohol use disorder with or without liver involvement; solid tumors of the lung, liver, esophagus, pancreas, and colorectum; and in hematological malignancies such as leukemia and bone marrow dysplasia.

Topics: Alcoholism; Anemia, Megaloblastic; Animals; Female; Pregnancy; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins

Imerslund-Gräsbeck syndrome (IGS) is a rare autosomal recessive disorder characterized by vitamin B12 malabsorption. Most patients present with non-specific symptoms attributed to vitamin B12 deficiency, and proteinuria. Patients may if untreated, develop severe neurocognitive manifestations. If recognized and treated with sufficient doses of vitamin B12, patients recover completely. We provide, for the first time, an overview of all previously reported cases of IGS. In addition, we provide a complete review of IGS and describe two new patients.

Topics: Anemia, Megaloblastic; Humans; Proteinuria; Vitamin B 12; Vitamin B 12 Deficiency

In this review of megaloblastic anemia (MA), an overview of vitamin B

Topics: Anemia, Megaloblastic; Folic Acid; Folic Acid Deficiency; Humans; Infant; Infant, Newborn; Vitamin B 12; Vitamin B 12 Deficiency

Vitamin B12 is assimilated and transported by complex mechanisms that involve three transport proteins, intrinsic factor (IF), haptocorrin (HC) and transcobalamin (TC) and their respective membrane receptors. Vitamin deficiency is mainly due to inadequate dietary intake in vegans, and B12 malabsorption is related to digestive diseases. This review explores the physiology of vitamin B12 absorption and the mechanisms and diseases that produce malabsorption. In the stomach, B12 is released from food carrier proteins and binds to HC. The degradation of HC by pancreatic proteases and the pH change trigger the transfer of B12 to IF in the duodenum. Cubilin and amnionless are the two components of the receptor that mediates the uptake of B12 in the distal ileum. Part of liver B12 is excreted in bile, and undergoes an enterohepatic circulation. The main causes of B12 malabsorption include inherited disorders (Intrinsic factor deficiency, Imerslund-Gräsbeck disease, Addison's pernicious anemia, obesity, bariatric surgery and gastrectomies. Other causes include pancreatic insufficiency, obstructive Jaundice, tropical sprue and celiac disease, bacterial overgrowth, parasitic infestations, Zollinger-Ellison syndrome, inflammatory bowel diseases, chronic radiation enteritis of the distal ileum and short bowel. The assessment of B12 deficit is recommended in the follow-up of subjects with bariatric surgery. The genetic causes of B12 malabsorption are probably underestimated in adult cases with B12 deficit. Despite its high prevalence in the general population and in the elderly, B12 malabsorption cannot be anymore assessed by the Schilling test, pointing out the urgent need for an equivalent reliable test.

Topics: Adult; Aged; Anemia, Megaloblastic; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Vitamin B 12; Vitamin B 12 Deficiency

Black cohosh is a readily available dietary supplement currently marketed as a remedy for dysmenorrhea and menopausal symptoms and is one of the top-selling herbal supplements in the United States. Black cohosh extract (BCE) was nominated to the National Toxicology Program (NTP) by the National Cancer Institute and the National Institute of Environmental Health Sciences due to its widespread use and lack of animal toxicity studies. Results of the NTP BCE subchronic mouse toxicity study revealed a dose-dependent, non-regenerative decrease in the erythron with an increase in the mean corpuscular volume (macrocytosis). Howell-Jolly bodies, or micronuclei, were significantly increased. These particular changes indicated an ineffective erythropoiesis consistent with a condition known as megaloblastic anemia. Megaloblastic anemia is due to disruptions in DNA synthesis during hematopoiesis and can be a result of an inherited or drug-induced disorder or a consequence of folate or cobalamin deficiency. Subsequent mouse studies revealed hematological and biochemical changes that were consistent with a functional cobalamin deficiency. This article will review basic mechanisms and laboratory features of megaloblastic anemia. The results of our studies including morphological abnormalities of the erythron and biomarkers of folate and cobalamin deficiencies, as well as hepatic microarray gene changes, are also discussed.

Topics: Anemia, Megaloblastic; Animals; Cimicifuga; Female; Folic Acid; Mice; Mice, Inbred Strains; Plant Extracts; Vitamin B 12; Vitamin B 12 Deficiency

Megaloblastic anemia causes macrocytic anemia from ineffective red blood cell production and intramedullary hemolysis. The most common causes are folate (vitamin B

Topics: Adolescent; Aged; Anemia, Megaloblastic; Avitaminosis; Diagnosis, Differential; Dietary Supplements; Female; Folic Acid; Folic Acid Deficiency; Humans; Male; Severity of Illness Index; Vitamin B 12; Vitamin B 12 Deficiency

Immune dysfunction, including severe combined immunodeficiency, has been described in genetic disorders affecting the metabolism of the vitamins cobalamin (vitamin B12) and folate. We have reviewed reports of clinical findings in patients with a number of inborn errors of cobalamin or folate metabolism, specifically looking for immune problems.. There is little evidence that immune function is affected in most of the disorders. Exceptions are Imerslund-Gräsbeck syndrome and hereditary folate malabsorption (affecting intestinal absorption of cobalamin and folate, respectively), transcobalamin deficiency (affecting transport of cobalamin in blood and cellular cobalamin uptake), and methylenetetrahydrofolate dehydrogenase 1 deficiency (catalyzing cytoplasmic interconversion of reduced folate coenzyme derivatives).. Although some inborn errors of cobalamin or folate can be associated with immune dysfunction, the degree and type of immune dysfunction vary with no obvious pattern.

Topics: Anemia, Megaloblastic; Folic Acid; Folic Acid Deficiency; Humans; Malabsorption Syndromes; Methylenetetrahydrofolate Dehydrogenase (NADP); Minor Histocompatibility Antigens; Nutritional Physiological Phenomena; Primary Immunodeficiency Diseases; Proteinuria; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Homocysteine (Hcy) is methylated by methionine synthase to form methionine with methyl-cobalamin as a cofactor. The reaction demethylates 5-methyltetrahydrofolate to tetrahydrofolate, which is required for DNA and RNA synthesis. Deficiency of either of the cobalamin (Cbl) and/or folate cofactors results in elevated Hcy and megaloblastic anemia. Elevated Hcy is a sensitive biomarker of Cbl and/or folate status and more specific than serum vitamin assays. Elevated Hcy normalizes when the correct vitamin is given. Elevated Hcy is associated with alcohol use disorder and drugs that target folate or Cbl metabolism, and is a risk factor for thrombotic vascular disease. Elevated methionine and cystathionine are associated with liver disease. Elevated Hcy, cystathionine, and cysteine, but not methionine, are common in patients with chronic renal failure. Higher cysteine predicts obesity and future weight gain. Serum S-adenosylhomocysteine (AdoHcy) is elevated in Cbl deficiency and chronic renal failure. Drugs that require methylation for catabolism may deplete liver S-adenosylmethionine and raise AdoHcy and Hcy. Deficiency of Cbl or folate or perturbations of their metabolism cause major changes in sulfur amino acids.

Topics: Alcoholism; Amino Acids, Sulfur; Anemia, Megaloblastic; Biomarkers; Cardiovascular Diseases; Folic Acid; Folic Acid Deficiency; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Liver Diseases; Nutritional Status; Obesity; S-Adenosylhomocysteine; Vitamin B 12; Vitamin B 12 Deficiency

B

Topics: Anemia, Megaloblastic; Anemia, Pernicious; Animals; Folic Acid; Humans; Intestinal Absorption; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Megaloblastic; DNA; Folic Acid; Gastrointestinal Absorption; Humans; Purines; Pyrimidines; Thymine Nucleotides; Vitamin B 12; Vitamin B 12 Deficiency

Cobalamin (vitamin B12) deficiency is a common cause of megaloblastic anemia in Western populations. Laboratory evaluation of megaloblastic anemia frequently includes the assessment of patient cobalamin and folate status. Current total serum cobalamin measurements are performed in the clinical laboratory with competitive binding luminescence assays, whose results may not always accurately reflect actual cobalamin stores. Surrogate markers of cobalamin deficiency such as methylmalonic acid and homocysteine have been utilized to improve diagnostic accuracy; however, the specificity of these tests by themselves is rather low. Measurement of the biologically active fraction of cobalamin, holotranscobalamin, has been proposed as a replacement for current total cobalamin assays. Although holotranscobalamin measurements appear to have slighter better sensitivity, the specificity of this assay remains to be determined. The relative merits and demerits of commonly available methods to assess cobalamin deficiency in patients with suspected megaloblastic anemia are discussed.

Topics: Anemia, Megaloblastic; Humans; Vitamin B 12; Vitamin B 12 Deficiency

Imerslund-Gräsbeck syndrome is a rare autosomal recessive disorder, characterized by vitamin B12 deficiency due to selective malabsorption of the vitamin and usually results in megaloblastic anemia appearing in childhood. It is responsive to parenteral vitamin B12 therapy.The estimated prevalence (calculated based on Scandinavian data) is less than 6:1,000,000. However, many cases may be misdiagnosed.When there is reasonable evidence to suspect that a patient suffers from IGS, a new and straightforward approach to diagnosis is mutational analysis of the appropriate genes. We report for the first time the case of a girl of Italian ancestry with IGS genetically confirmed by the detection of a homozygous missense mutation in the AMN gene (c.208-2 A > G).

Topics: Anemia, Megaloblastic; Child, Preschool; DNA Mutational Analysis; Female; Follow-Up Studies; Genetic Predisposition to Disease; Homozygote; Humans; Italy; Malabsorption Syndromes; Membrane Proteins; Mutation, Missense; Proteins; Proteinuria; Rare Diseases; Risk Assessment; Severity of Illness Index; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency

In our pioneering work in 1956, two binders of vitamin B12 (B12) alias cobalamin (Cbl) were identified in gastric juice, S with slow electrophoretic mobility, a 70 kD protein with intrinsic factor (IF) activity and another rapid (R), not IF active but probable digestion product. Numerous sources contained a protein immunologically identical to R (haptocorrin, Hc). Another IF-active component (I) was found. Isoelectric focusing showed that S, I and R were assemblies of "isoproteins" with different pI's due to varying glycosidation. Isolation of S, I and R in microquantities was achieved in 1962 using a series of ion exchange chromatographies and gel filtration. Ponderable products were obtained in 1965-1966. The B12-IF complex was a dimer, contained 13% carbohydrate and showed a different absorption spectrum than B12. Using the Schilling test, B12 absorption was shown to require Ca(++), bound in vitro to the ileal receptor and IF, but most of Ca(++) could be removed with sialidase. The receptor-substrate complex contained Ca(++) and carbohydrate. The purified receptor was shown to contain two main subunits. The Imerslund-Gräsbeck syndrome was discovered 1958-1960; it is caused by mutations in either of two genes, cubilin or amnionless, which form the multiligand receptor cubam. Testicular biopsies during and after B12-treated deficiency showed remarkable improvement after therapy. Studies of the turnover of radioactive B12 revealed biliary and fecal excretion, enterohepatic circulation and allowed calculation of biological half-life and daily need. The B12 coenzymes largely behaved like B12. To study whether radiocobalt in B12 was representative of the rest of the B12 molecule, (32)P and (57)Co labeled hydroxocobalamins were biosynthesized and shown to behave identically when given simultaneously to rats. The complex metabolism of B12 explains the pathogenesis of B12 deficiencies. Some of its mechanisms are not restricted to B12, e.g. the endocytosis of B12-IF also applies to other macromolecules.

Topics: Anemia, Megaloblastic; Animals; Gastric Juice; Humans; Intrinsic Factor; Malabsorption Syndromes; Proteinuria; Vitamin B 12; Vitamin B 12 Deficiency

The usual dietary sources of vitamin B(12) are animal foods, meat, milk, egg, fish, and shellfish. As the intrinsic factor-mediated intestinal absorption system is estimated to be saturated at about 1.5-2.0 microg per meal under physiologic conditions, vitamin B(12) bioavailability significantly decreases with increasing intake of vitamin B(12) per meal. The bioavailability of vitamin B(12) in healthy humans from fish meat, sheep meat, and chicken meat averaged 42%, 56%-89%, and 61%-66%, respectively. Vitamin B(12) in eggs seems to be poorly absorbed (< 9%) relative to other animal food products. In the Dietary Reference Intakes in the United States and Japan, it is assumed that 50% of dietary vitamin B(12) is absorbed by healthy adults with normal gastro-intestinal function. Some plant foods, dried green and purple lavers (nori) contain substantial amounts of vitamin B(12), although other edible algae contained none or only traces of vitamin B(12). Most of the edible blue-green algae (cyanobacteria) used for human supplements predominantly contain pseudovitamin B(12), which is inactive in humans. The edible cyanobacteria are not suitable for use as vitamin B(12) sources, especially in vegans. Fortified breakfast cereals are a particularly valuable source of vitamin B(12) for vegans and elderly people. Production of some vitamin B(12)-enriched vegetables is also being devised.

Topics: Anemia, Megaloblastic; Animals; Biological Availability; Fishes; Food Analysis; Humans; Meat; Milk; Shellfish; Tea; Vegetables; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Megaloblastic; DNA; Folic Acid; Humans; Time Factors; Vitamin B 12

Imerslund-Gräsbeck syndrome (IGS) or selective vitamin B(12) (cobalamin) malabsorption with proteinuria is a rare autosomal recessive disorder characterized by vitamin B(12) deficiency commonly resulting in megaloblastic anemia, which is responsive to parenteral vitamin B(12) therapy and appears in childhood. Other manifestations include failure to thrive and grow, infections and neurological damage. Mild proteinuria (with no signs of kidney disease) is present in about half of the patients. Anatomical anomalies in the urinary tract were observed in some Norwegian patients. Vitamin B(12) absorption tests show low absorption, not corrected by administration of intrinsic factor. The symptoms appear from 4 months (not immediately after birth as in transcobalamin deficiency) up to several years after birth. The syndrome was first described in Finland and Norway where the prevalence is about 1:200,000. The cause is a defect in the receptor of the vitamin B(12)-intrinsic factor complex of the ileal enterocyte. In most cases, the molecular basis of the selective malabsorption and proteinuria involves a mutation in one of two genes, cubilin (CUBN) on chromosome 10 or amnionless (AMN) on chromosome 14. Both proteins are components of the intestinal receptor for the vitamin B(12)-intrinsic factor complex and the receptor mediating the tubular reabsorption of protein from the primary urine. Management includes life-long vitamin B(12) injections, and with this regimen, the patients stay healthy for decades. However, the proteinuria persists. In diagnosing this disease, it is important to be aware that cobalamin deficiency affects enterocyte function; therefore, all tests suggesting general and cobalamin malabsorption should be repeated after abolishment of the deficiency.

Topics: Adolescent; Anemia, Megaloblastic; Animals; Child; Child, Preschool; Diagnosis, Differential; Dogs; Finland; Humans; Infant; Malabsorption Syndromes; Models, Animal; Norway; Prevalence; Prognosis; Proteinuria; Rare Diseases; Syndrome; Vitamin B 12; Vitamin B 12 Deficiency

Pernicious anemia is a common cause of megaloblastic anemia throughout the world and especially in persons of European or African descent. Dietary deficiency of vitamin B12 due to vegetarianism is increasing and causes hyperhomocysteinemia. The breast-fed infant of a vitamin B12-deficient mother is at risk for severe developmental abnormalities, growth failure, and anemia. Elevated methylmalonic acid and/or total homocysteine are sensitive indicators of vitamin B12-deficient diets and correlate with clinical abnormalities. Dietary vitamin B12 deficiency is a severe problem in the Indian subcontinent, Mexico, Central and South America, and selected areas in Africa. Dietary vitamin B12 deficiency is not prevalent in Asia, except in vegetarians. Areas for research include intermittent vitamin B12 supplement dosing and better measurements of the bioavailability of B12 in fermented vegetarian foods and algae.

Topics: Anemia, Megaloblastic; Anemia, Pernicious; Biological Availability; Diet, Vegetarian; Global Health; Humans; Hyperhomocysteinemia; Intestinal Absorption; Vitamin B 12; Vitamin B 12 Deficiency

Four patients, three women aged 49, 47 and 74 years, and a man aged 64 years, presented with progressive sensory deficit, pyramidal tract symptoms and postural instability. Tests revealed megaloblastic anaemia and low vitamin B12 levels. Two of the female patients had undergone gynaecological surgery with nitrous oxide anaesthesia, and the male patient had undergone a gastric resection. Subacute combined degeneration of the spinal cord is a neurological disease based on vitamin B12 deficiency. It involves the posterior and lateral columns of the spinal cord, and sometimes the peripheral nerves, the optic nerve or the brain. An MRI scan of the cervical cord revealed abnormalities for three of the four patients. Following parenteral supplementation of vitamin B12, the symptoms and the MRI abnormalities either disappeared or significantly improved. Vitamin B12 deficiency can cause subacute combined degeneration of the cord by interfering with myelin synthesis. As vitamin B12 deficiency is caused by malabsorption in the gastrointestinal tract, oral supplementation is insufficient. It is essential to recognise this treatable disease at an early stage, and not to reject the possible diagnosis if the MRI findings are abnormal. Simple blood tests can lead to the diagnosis and to effective treatment.

Topics: Aged; Anemia, Megaloblastic; Anesthetics; Cervical Vertebrae; Female; Humans; Injections, Intramuscular; Magnetic Resonance Imaging; Malabsorption Syndromes; Male; Middle Aged; Myelin Sheath; Nitrous Oxide; Spinal Cord; Spinal Cord Diseases; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency

Classically, deficiency of folic acid (folate) or vitamin B12 (cobalamin) was recognized by the presence of a macrocytic anemia resulting from megaloblastic changes in the bone marrow. A markedly changing paradigm has identified both new mechanisms for altered folate and cobalamin status and new sequelae and clinical interrelationships that include altered mechanisms of absorption, a changing pattern of neurologic deficits, an increased risk of vascular occlusive lesions, and an important relationship with the mechanisms of neoplastic transformation. Several of these newer characterizations relate to issues of neoplasia in the nonpregnant woman and to issues in pregnancy, such as the potential for developmental abnormalities of the fetal nervous system.

Topics: Anemia, Megaloblastic; Anemia, Pernicious; Female; Folic Acid; Folic Acid Deficiency; Humans; Hyperhomocysteinemia; Neoplasms; Neural Tube Defects; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic; Vascular Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Megaloblastic; Diagnosis, Differential; Humans; Immune System Diseases; Metabolism, Inborn Errors; Methylmalonic Acid; Methylmalonyl-CoA Mutase; Neutropenia; Prognosis; Vitamin B 12

Topics: Anemia, Megaloblastic; Folic Acid; Folic Acid Deficiency; Humans; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Megaloblastic; Biomarkers; Diagnosis, Differential; Homocysteine; Humans; Infant; Mutation; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Functional methionine synthase deficiency due to abnormal methylcobalamin metabolism causes megaloblastic anemia, moderate to severe developmental delay, lethargy, and anorexia in association with homocystinuria. Patients with this disorder of cobalamin metabolism can be classified into two separate groups, cblE or cblG, primarily on the basis of complementation analysis with cultured skin fibroblasts. We describe two unrelated boys, ages 3 and 5 years, with the cblG defect in methylcobalamin synthesis. Both children presented with severe developmental delay, lethargy, anorexia, and megaloblastic anemia. The diagnosis of homocystinuria was delayed in each case due to difficulties with detection of small amounts of homocystine in physiologic samples. The clinical course of cblG disease is favorably altered by treatment with intramuscular hydroxycobalamin. Megaloblastosis in the presence of adequate supplies of cobalamin and folate in the blood must alert the clinician to the possibility of functional methionine synthase deficiency and should prompt a careful search for associated biochemical hallmarks, including homocystinuria/emia.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Anemia, Macrocytic; Anemia, Megaloblastic; Anorexia; Child, Preschool; Developmental Disabilities; Female; Fibroblasts; Genetic Complementation Test; Homocystine; Homocystinuria; Humans; Male; Methionine; Skin; Vitamin B 12

The review of the literature data and the evidence obtained on 85 own patients with B12-deficiency anemia concerning iron metabolism underlie 3 variants proposed by the authors: pronounced manifestations of secondary sideroachresia before B12 therapy, utilization iron deficiency upon B12 introduction, dimorphic anemia (development of megaloblastic erythropoiesis in prior iron deficiency). The causes of megaloblastic erythropoiesis incompetence (slow rate, hemolytic component, secondary sideroachresia) are discussed.

Topics: Anemia, Iron-Deficiency; Anemia, Megaloblastic; Erythropoiesis; Female; Humans; Iron; Iron Deficiencies; Male; Megaloblasts; Middle Aged; Vitamin B 12; Vitamin B 12 Deficiency

The case of a 15-month-old, strictly breast-fed infant whose mother had been following a vegetarian diet for ten years is reported. The infant had severe megaloblastic anemia with an arrest in growth, hypotonia, and failure of psychomotor development. The very low levels of vitamin B12 in the infant's serum and mother's milk confirmed the diagnosis. Management of such cases consists in administration of vitamin B12 supplements, with a blood transfusion if needed. Other concomitant deficiencies should be looked for. The outcome is rapidly favorable. The patient reported here is now four years of age and has normal statural growth and psychomotor development.

Topics: Anemia, Megaloblastic; Breast Feeding; Diet, Vegetarian; Female; Humans; Infant; Vitamin B 12

Topics: Anemia, Megaloblastic; Humans; Intrinsic Factor; Nervous System Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Macrocytic and/or megaloblastic anaemias of infants and children are more often due to a defective bone marrow production than to haemolysis. They are mostly related to folate and/or cobalamin deficiency or to a disturbance in the metabolism of one of these vitamins (enzyme deficiencies or defect of synthesis of their active forms). More rarely, these anaemias are associated with congenital deficiency of the enzymes involved in pyrimidine or purine biosynthesis. A few cases of thiamine-responsive megaloblastic anaemia have been reported. Some blood diseases may also associated with macrocytic anaemia. Finally, many drugs (antifolic agents, antipurine or antipyrimidine compounds) may induce macrocytic anaemia.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Folic Acid; Folic Acid Deficiency; Humans; Infant; Vitamin B 12; Vitamin B 12 Deficiency

Functional methionine synthase deficiency is generally characterized by homocystinuria and hypomethioninemia in the absence of methylmalonic aciduria. Patients are divided into two classes, cblE and cblG, on the basis of complementation analysis. Presentation has usually been in the first 2 years of life, but one patient came to medical attention at age 21 years with symptoms initially diagnosed as multiple sclerosis. Common findings among 11 patients (4 with cblE and 7 with cblG) have included megaloblastic anemia (all patients) and various neurological deficits including developmental retardation (10 patients), cerebral atrophy (8 patients), hypotonia (7 patients), EEG abnormalities (6 patients), and nystagmus (5 patients). Hypertonia, seizures, blindness, and ataxia were less frequent. All patients have responded to therapy with cobalamin with resolution of anemia and biochemical abnormalities; neurological deficits resolved more slowly and in some cases incompletely. Hydroxycobalamin has been more effective than cyanocobalamin. Fibroblasts from patients with cblE (5 patients) and cblG (6 patients) all showed decreased intracellular levels of methylcobalamin (MeCbl) and decreased incorporation of label from 5-methyltetrahydrofolate into macromolecules, suggesting decreased activity of the MeCbl-dependent enzyme methionine synthase. Methionine synthase specific activity in extracts of all cblE fibroblasts was normal or near-normal under standard reducing conditions; synthase specific activity in extracts of 5 cblG patients was low but was high in a 6th patient measured in another laboratory. Thus, there is heterogeneity among patients with functional methionine synthase deficiency both in clinical presentation and in the results of biochemical studies of cultured cells.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Adult; Anemia, Megaloblastic; Cells, Cultured; Female; Fibroblasts; Genetic Complementation Test; Homocystinuria; Humans; Infant; Infant, Newborn; Male; Methionine; Methyltransferases; Nervous System Diseases; Vitamin B 12

Cobalamin deficiency leads to impaired folate function as demonstrated by markedly impaired single-carbon unit transfer into purine, thymidine and methionine. This occurs in the total absence of 'methylH4folate trapping'. In cobalamin deficiency there is impaired synthesis of formylH4folate and raised levels of endogenous formate in blood and liver. FormylH4folate and methionine reverse the effects of cobalamin deficiency. Methionine provides formate via its metabolism to methylthioribose. Recently it has been suggested that the neuropathy of cobalamin deficiency is due to impaired methylation but this was not confirmed. It is likely that defects demonstrated in marrow and liver are also the explanation for the effects of cobalamin deficiency in the CNS.

Topics: Anemia, Megaloblastic; Animals; Central Nervous System Diseases; Coenzymes; Folic Acid; Folic Acid Deficiency; Formates; Humans; Methionine; Models, Biological; Tetrahydrofolates; Thymidine; Vitamin B 12; Vitamin B 12 Deficiency

Three cases of vitamin B12 deficiency that occurred during infancy are presented. These cases appeared to be the result of pre-existing maternal deficiency. All three infants demonstrated evidence of neurodevelopmental delay at presentation, and one had sustained loss of milestones and developed involuntary motor movements. Prior to the initiation of therapy, all three infants were anemic: one was thrombocytopenic and one pancytopenic. In all three cases the hematologic and neurologic abnormalities were corrected with vitamin B12 therapy. The literature is reviewed and discussed with respect to the mechanism of the infants' vitamin B12 deficiency and neurodevelopmental manifestations.

Topics: Anemia, Megaloblastic; Anemia, Pernicious; Breast Feeding; Child, Preschool; Diet, Vegetarian; Female; Humans; Infant; Infant Nutrition Disorders; Male; Maternal-Fetal Exchange; Milk, Human; Pregnancy; Pregnancy Complications, Hematologic; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Animals; Folic Acid; Formates; Humans; Macrophages; Rats; Tuberculosis; Vitamin B 12; Vitamin B 12 Deficiency

Developments relating to cobalamin and folate are reviewed. Current work on the relations between these two coenzymes are discussed, particularly those that have emerged in studies using nitrous oxide, which inactivates cobalamin.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Folic Acid; Humans; Intestinal Absorption; Vitamin B 12

Topics: Aged; Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Folic Acid; Folic Acid Deficiency; Humans; Vitamin B 12; Vitamin B 12 Deficiency

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Anemia, Megaloblastic; Animals; Central Nervous System; Deoxyuridine; Disease Models, Animal; Drug Interactions; Enzyme Activation; Folic Acid; Folic Acid Deficiency; Histidine; Humans; Liver; Methionine; Methylmalonyl-CoA Mutase; Nitrous Oxide; Oxidation-Reduction; Pteroylpolyglutamic Acids; Purines; Serine; Tetrahydrofolates; Thymidylate Synthase; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adult; Aged; Anemia, Hypochromic; Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Child; Child, Preschool; Demyelinating Diseases; Diagnosis, Differential; Female; Folic Acid; Folic Acid Deficiency; Humans; Infant; Middle Aged; Pregnancy; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Megaloblastic; Animals; Female; Folic Acid; Folic Acid Deficiency; Formiminoglutamic Acid; Humans; Infant; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Male; Nutritional Requirements; Pregnancy; Pregnancy Complications, Hematologic; Vitamin B 12; Vitamin B 12 Deficiency

This review focusses on research performed by the author and coworkers. The absorption, turnover and excretion of cobalamin and the pathogenesis of cobalamin deficiency states are described and the laboratory tests used to diagnose these states are discussed. Topics dealt with in detail include: overall turnover, daily need, enterohepatic circulation and excretion of cobalamin and other corrins . The soluble proteins mediating cobalamin transport and their cellular receptors are described and their nomenclature, isolation, structure and mode of action, the role of calcium in the membrane transport, the evolution of these systems and the analogies with transport systems for other substrates are discussed together with deficiency states, especially fish tapeworm anemia and familial selective vitamin B12 malabsorption with proteinuria. Folate deficiency is a relatively rare cause of megaloblastic anemia in Scandinavia but common in North America and explanations for this difference are suggested. The methods of assaying cobalamin in serum and plasma and the performance of radiovitamin B12 absorption tests are critically evaluated. The measurement of intrinsic factor in gastric juice, serum, amniotic fluid and urine is described.

Topics: Anemia, Megaloblastic; Anemia, Pernicious; Biological Transport; Corrinoids; Diet; Diphyllobothriasis; Endocytosis; Erythrocyte Indices; Folic Acid; Humans; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Membrane Transport Proteins; Metabolic Clearance Rate; Receptors, Cell Surface; Receptors, Peptide; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Megaloblastic; Animals; Deoxyuridine; Folic Acid; Formates; Hematopoiesis; Humans; Methylation; Nitrous Oxide; Vitamin B 12

Topics: Anemia, Megaloblastic; Blood Volume; Erythrocyte Indices; Female; Folic Acid; Hematinics; Humans; Infant; Infant, Newborn; Iron; Iron Deficiencies; Nutritional Requirements; Postpartum Period; Pregnancy; Pregnancy Complications; Vitamin B 12

Women who use oral contraceptives have impaired folate metabolism as shown by slightly but significantly lower levels of folate in the serum and the erythrocytes and an increased urinary excretion of formiminoglutamic acid. The vitamin B12 level in their serum is also significantly lower than that of control groups. However, there is no evidence of tissue depletion of vitamin B12 associated with the use of oral contraceptives. The causes and clinical significance of the impairment of folate and vitamin B12 metabolism in these women is discussed in this review of the literature. Clinicians are advised to ensure that women who shop taking "the pill" because they wish to conceive have adequate folate stores before becoming pregnant.. The effects of oral contraception (OC) on folate and vitamin B12 metabolism are a subject of much controversy. Many studies indicate that OCs impair folate metabolsim and produce some degree of folate depletion, as demonstrated by slight but significant lower levels of folate in the serum and the erythrocytes, and by an increased urinary excretion of formiminoglutamic acid. These effects are unlikely to cause anemia or megalobastic changes in women who have a good dietary intake of folate. Since pregnant women are predisposed to the development of folate deficiency, it would be necessary when stopping the pill for desire of pregnancy to take folate supplements before becoming pregnant. OCs may also produce a low serum level of vitamin B12; this effect, however, is not associated with evidence of tissue depletion of vitamin B12, and does not have any great clinical significance; the effect may also be caused by vitamin B12 malabsorption rather than by OC treatment.

Topics: Anemia, Megaloblastic; Contraceptives, Oral; Erythrocyte Indices; Female; Folic Acid; Folic Acid Deficiency; Formiminoglutamic Acid; Hematocrit; Hemoglobins; Humans; Pregnancy; Vitamin B 12

Topics: Adolescent; Adult; Anemia, Megaloblastic; Blood Platelets; Bone Marrow Cells; Bone Marrow Transplantation; Child; Factor VIII; Hematologic Diseases; Hematopoietic Stem Cells; Hemophilia A; Humans; Leukemia; Thalassemia; Vitamin B 12; von Willebrand Diseases

A review of nutritional anaemia in Africa is presented above. It has been noted that nutritional anaemia, including iron-deficiency anaemia, megaloblastic anaemia due to folate deficiency or vitamin B12 deficiency, or both, and protein deficiency-anaemia, is widespread throughout Africa. It is particularly common in growing children, women of child-bearing age, pregnant women and lactating mothers. The anaemia is also especially common during the second half of the dry season and the first half of the wet season, when food supplies are limited. In all cases the anaemia is caused either by limited dietary intake, excessive loss of nutrients or excessive utilization. The anaemia is associated with a number of sequelae including both structural changes, like mitochondrial swelling and mucosal atrophy, and functional abnormalities, such as cardiac failure, decreased work output, increased pregnancy risks and increased susceptibility to infections. The evidence in favour of increased susceptibility to infections in megaloblastic anaemia and protein-deficiency anaemia is overwhelming, but in iron-deficiency anaemia the available information argues in favour of reduced susceptibility to infections, except after initiation of iron therapy. The treatment of nutritional anaemia includes replacement of the deficient nutrients (and blood transfusion in severe cases), prevention of further nutrient losses and treatment of associated complications.

Topics: Adult; Africa; Anemia; Anemia, Hypochromic; Anemia, Megaloblastic; Child; Deficiency Diseases; Female; Folic Acid; Folic Acid Deficiency; Humans; Iron; Male; Pregnancy; Protein Deficiency; Tropical Climate; Vitamin B 12; Vitamin B 12 Deficiency

The diagnosis of megaloblastic anemia and the differentiation of folate and vitamin B12 deficiency require, in addition to careful attention to the history and physical findings, the use of laboratory tests. In this paper the commonly ordered tests for such a diagnosis are discussed, with emphasis on the conditions that may cause false-positive or false-negative results in the complete blood count, examination of a peripheral blood smear and a bone marrow specimen, serum and erythrocyte folate assays, serum vitamin B12 assays, tests of vitamin B12 absorption and gastric analysis.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Anemia, Sideroblastic; Biological Assay; Blood Cell Count; Bone Marrow Examination; Diagnostic Errors; Erythrocytes; Folic Acid; Folic Acid Deficiency; Humans; Lacticaseibacillus casei; Schilling Test; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adult; Anemia, Macrocytic; Anemia, Megaloblastic; Anticonvulsants; Blood Cell Count; Child, Preschool; Contraceptives, Oral; Diagnosis, Differential; Diet; Erythropoiesis; Ethanol; Female; Folic Acid; Folic Acid Antagonists; Folic Acid Deficiency; Humans; Male; Medical History Taking; Methionine Adenosyltransferase; Vitamin B 12; Vitamin B 12 Deficiency

The three most common causes of macrocytosis--vitamin B12 or folate deficiency, liver disease, and reticulocytosis--usually can be differentiated on the basis of red cell indexes and morphologic findings. Bone marrow studies are not indicated. In reticulocytosis, the mean corpuscular volume (MCV) rarely exceeds ll0 cu mu and a reticulocyte count quickly establishes the diagnosis. In liver disease, macrocytosis is also mild and uniform. The RBCs are round. In megaloblastic anemia, the MCV may exceed 150 cu mu. The RBCs vary considerably in size and shape. The macrocytes tend to be oval. Serum vitamin B12 determination remains the best test for unmasking vitamin B12 deficiency. It should be ordered in conjunction with serum and red cell folate determinations in the course of investigating a macrocytic anemia. When vitamin B12 deficiency has been established, a Schilling test or plasma uptake test is indicated to pinpoint the cause.

Topics: Aged; Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Sideroblastic; Clinical Laboratory Techniques; Erythrocytes; Folic Acid; Humans; Liver Diseases, Alcoholic; Male; Radioisotopes; Schilling Test; Vitamin B 12

Topics: Anemia, Megaloblastic; Australia; Child; Humans; Malabsorption Syndromes; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Alcoholism; Anemia, Macrocytic; Anemia, Megaloblastic; Anti-Bacterial Agents; Anticonvulsants; Antimetabolites, Antineoplastic; Contraceptives, Oral; Drug-Related Side Effects and Adverse Reactions; Folic Acid Antagonists; Humans; Malabsorption Syndromes; Pyrimethamine; Triamterene; Trimethoprim; Vitamin B 12

Topics: Anemia; Anemia, Hemolytic; Anemia, Hemolytic, Congenital; Anemia, Hypochromic; Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Sideroblastic; Chronic Disease; Diagnosis, Differential; Humans; Malabsorption Syndromes; Thalassemia; Vitamin B 12

Effective inhibition of cell division by anesthetics occurs only when cells are exposed to concentrations more than twice those required for anesthesia. Neutropenia following prolonged inhalation of nitrous oxide seems to be caused by a different mechanism, in which the cobalt in B12 is oxidised to the trivalent form by chemical reaction with nitrous oxide. B12 is thereby inactivated and this interferes with folate metabolism and thymidine synthesis: the effect may be detected after only a few hours in vivo exposure of mammals to 50% nitrous oxide. Unlike lymphocytes, the random motility of human neutrophils is not decreased by in vitro exposure to concentrations of halothane required for anesthesia. Similarly there is no effect on chemotaxis to casein and phagocytosis with exposure up to 2% halothane.

Topics: Anemia, Megaloblastic; Anesthetics; Animals; Bone Marrow; Cell Movement; Chemotaxis, Leukocyte; Halothane; Humans; Liver; Methionine; Neutropenia; Neutrophils; Nitrous Oxide; Phagocytosis; Rats; Spinal Cord; Thymidine; Vitamin B 12

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Antibodies; Cobalt Radioisotopes; Deoxyuridine; Folic Acid; Humans; Intestinal Absorption; Intrinsic Factor; Isotope Labeling; Protein Binding; Radioimmunoassay; Transcobalamins; Vitamin B 12

Subnormal red-cell folate values were encountered in 20 of 63 thalassaemic subjects in a population with a low incidence of megaloblastosis. The abnormality was not associated with haematological changes of megaloblastosis and could not be explained on the basis of incomplete liberation of intra-erythrocytic folates, serum conjugase deficiency of vitamin B12 deficiency. Evidence is presented to indicate that it is unlikely to represent a state of subclinical folate deficiency. The exact cause of the abnormality is unknown.

Topics: Anemia, Megaloblastic; Bone Marrow; Bone Marrow Cells; Erythrocytes; Female; Folic Acid; Folic Acid Deficiency; gamma-Glutamyl Hydrolase; Hong Kong; Humans; Male; Thalassemia; Vitamin B 12

Topics: Adolescent; Amino Acid Metabolism, Inborn Errors; Anemia, Megaloblastic; Child; Female; Folic Acid; Galactosemias; Glutamate Decarboxylase; Homocystinuria; Humans; Infant; Infant, Newborn; Lactose Intolerance; Maple Syrup Urine Disease; Metabolism, Inborn Errors; Methylmalonic Acid; Phenylketonurias; Pregnancy; Vitamin B 12

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Anti-Bacterial Agents; Anticonvulsants; Antimetabolites; Contraceptives, Oral; Ethanol; Folic Acid; Folic Acid Antagonists; Humans; Intestinal Absorption; Purines; Pyrimidines; Vitamin B 12

Topics: Adolescent; Adult; Anemia, Hemolytic; Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Biological Transport; Bone Marrow; Bone Marrow Cells; Child; Child, Preschool; Female; Folic Acid; Folic Acid Deficiency; Homocystinuria; Humans; Infant; Intrinsic Factor; Malabsorption Syndromes; Male; Metabolism, Inborn Errors; Methionine; Methionine Adenosyltransferase; Orotic Acid; Phenylketonurias; Tetrahydrofolate Dehydrogenase; Transcobalamins; Vitamin B 12

Topics: Adult; Aged; Anemia, Megaloblastic; Anticonvulsants; Blood-Brain Barrier; Brain; Brain Diseases; Child; Epilepsy; Erythrocytes; Female; Folic Acid; Folic Acid Deficiency; Formiminoglutamic Acid; Humans; Intellectual Disability; Male; Mental Disorders; Metabolism, Inborn Errors; Methotrexate; Middle Aged; Nervous System Diseases; Vitamin B 12; Vitamin B 12 Deficiency

1. Low serum B12 levels can be measured with considerable precision by microbiological assay with the Euglena gracilis assay and B12 deficiency can be recognised with a high level of consistency by either the Euglena or L. leichmannii assays. Either method is ideally suited for the assay of large numbers of specimens. The Lactobacillus leichmanii technique requires preliminary extraction of protein and it has been suggested that this may be a source of inaccuracy. 2. The radioisotope dilution assay should be the ideal method of measuring B12 levels in small or moderate numbers of specimens for it is a simple method that can be carried out in any laboratory with suitable counting equipment. After many false starts the conditions required for accurate assay are now understood. Each of 40 to 50 radioisotopic dilution techniques that have been introduced claims to be capable of differentiating B12 deficiency from control subjects but the reported correlations between the actual levels found in the two different assays are variable and the levels may be much higher with some radioisotopic methods. 3. The subnormal serum levels which are found in pernicious anaemia with all these techniques indicate severe reduction of the liver B12 level. A low serum B12 level in other conditions has, in the absence of associated folate or iron deficiency, the same significance. If the fall in the serum B12 level is associated with folate or iron deficiency, the tissue B12 levels are usually reduced but not to the low levels found in B12 deficiency states. 4. In practice, a subnormal B12 level is a valuable pointer not only to unsuspected pernicious anaemia but also to other gastrointestinal or nutritional disorders. The significance of a fall in the B12 level can only be understood if its cause is defined by a full clinical and gastroenterological investigation. 5. Falsely low serum B12 levels are found under certain iatrogenic conditions and B12 levels may be normal in spite of cellular deficiency of B12 under the rare circumstances of pernicious anaemia being associated with chronic myeloid leukaemia or when there is deficiency of TC 2.

Topics: Anemia, Megaloblastic; Anemia, Pernicious; Ascorbic Acid; Biological Assay; Bone Marrow; Bone Marrow Cells; Carrier Proteins; Deoxyuridine; Euglena gracilis; Female; Folic Acid Deficiency; Humans; Intrinsic Factor; Lactobacillus; Leukemia, Myeloid; Male; Pregnancy; Pregnancy Complications; Radioisotope Dilution Technique; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adolescent; Aged; Anemia, Macrocytic; Anemia, Megaloblastic; Female; Folic Acid Deficiency; Humans; India; Infant; Infant, Newborn; Infant, Premature; Lactation; Nutritional Physiological Phenomena; Nutritional Requirements; Pregnancy; Pregnancy Complications, Hematologic; United Kingdom; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Hemolytic; Anemia, Hypochromic; Anemia, Megaloblastic; Arthritis, Juvenile; Arthritis, Rheumatoid; Blood Volume; Collagen Diseases; Dermatomyositis; Felty Syndrome; Folic Acid; Hemolysis; Humans; Hyperplasia; Iron; Lupus Erythematosus, Systemic; Myositis; Polyarteritis Nodosa; Polymyalgia Rheumatica; Scleroderma, Systemic; Vitamin B 12

There is limited literature in children on efficacy of different routes of vitamin B12 administration for vitamin B12 deficiency macrocytic-megaloblastic anemia.. To compare parenteral with oral vitamin B12 therapy in children with macrocytic-megaloblastic anemia.. Single-center, open-label randomized controlled trial.. 80 children aged 2 month-18 year with clinical and laboratory features of nutritional macrocytic anemia.. All children received an initial single parenteral dose of 1000 µg vitamin B12 followed by randomization to either parenteral or oral vitamin B12 for subsequent doses. Group A was given 1000 µg intramuscular (IM) vitamin B12 (3 doses on alternate days for those aged <10 year, five doses for age >10 year), followed by monthly 1000 µg IM for the subsequent two doses. Group B was given daily oral vitamin B12 1500 µg (500 µg in <2 years age) for three months. Folic acid and iron supple-mentation, and relevant dietary advice were given to both groups in a similar fashion.. Improvement in serum vitamin B12 levels and total hemoglobin was compared three months post-treatment.. The median(IQR) increase in serum vitamin B12 level was significantly higher in group A [600 (389,775) vs 399 (313, 606) pg/mL; P= 0.016]. The median (IQR) rise of hemoglobin was also more in group A [2.7 (0.4,4.6) vs 0.5 (-0.1,1.2) g/dL; P=0.001].. Increase in serum vitamin B12 levels and hemoglobin was better in children with nutritional macrocytic anemia receiving parenteral as compared to oral vitamin B12.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Child; Folic Acid; Hemoglobins; Humans; Vitamin B 12; Vitamin B 12 Deficiency

Cobalamin (vitamin B12) deficiency, the most common cause of megaloblastic anemia, is treated with intramuscular (IM) cobalamin. It has been suggested by some investigators that oral (p.o.) cobalamin treatment may be as effective in the treatment of this condition, with the advantages of ease of administration and lower cost.. This study assessed the effects and cost of p.o. versus i.m. cobalamin treatment in patients with megaloblastic anemia due to cobalamin deficiency.. This was a 90-day, prospective, randomized, open-label study conducted at the Division of Hematology, Department of Internal Medicine, Adnan Menderes University Research and Practice Hospital (Aydin, Turkey). Patients aged > or =16 years with megaloblastic anemia due to cobalamin deficiency were randomized to receive 1000-microg cobalamin p.o. once daily for 10 days (p.o. group) or 1000-microg cobalamin i.m. once daily for 10 days (i.m. group). After 10 days, both treatments were administered once a week for 4 weeks, and after that, once a month for life. Patients were assessed for the presence of reticulocytosis between treatment days 5 and 10 until it was detected. Therapeutic effectiveness was assessed by measuring hematologic parameters on days 0, 10, 30, and 90 and serum vitamin B12 concentration on days 0 and 90. The Mini-Mental State Examination was used before and after the B12 therapy for cognitive function assessment and 125-Hz diapozone was used for vibration threshold testing. Neurologic sensory assessment, including soft-touch and pinprick examinations, was used to identify neuropathy at baseline and study end. Tolerability was assessed using laboratory tests and patient interview. Cost was assessed using the cost of the study drug and of the injection.. Sixty patients completed the study 26 in the p.o. group (16 men, 10 women; mean [SD] age, 60 [15] years) and 34 in the i.m. group (17 men, 17 women; mean [SD] age, 64 [10] years). Reticulocytosis was observed in all patients. In the p.o. group, at days 30 and 90, all hematologic parameters changed significantly versus day 0 (mean hemoglobin levels increased [both P<0.001]; mean corpuscular volume decreased [both P<0.001]; mean white blood cell count increased [day 30, P<0.01; day 90, P<0.001]; and mean platelet count increased [both P<0.001]). The mean serum vitamin B12 concentration increased significantly from day 0 to 90 (P<0.001). These hematologic parameters and the recovery patterns were similar between the 2 groups. Neurologic findings included sensitive peripheral neuropathy in 9 patients (15.0%), alteration of cognitive function (loss of memory, impaired concentration) in 7 patients (11.7%), and loss of sense of vibration in 5 patients (8.3%). Neurologic improvement was detected in 7 of 9 patients (77.8%) in the p.o. group and 9 of 12 patients (75.0%) in the i.m. group at day 30.. In this study of patients with megaloblastic anemia due to cobalamin deficiency, p.o. cobalamin treatment was as effective as i.m. cobalamin treatment. P.o. treatment also was better tolerated and less expensive compared with IM treatment. However, because of the small sample size and the short term of this study, further long-term studies are needed to determine the efficacy of p.o. cobalamin treatment.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anemia, Megaloblastic; Female; Hemoglobins; Humans; Injections, Intramuscular; Male; Middle Aged; Prospective Studies; Reticulocyte Count; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency

Ninety-five patients who had megaloblastic anaemia, and who lived in a subtropical climate, were studied to elucidate the importance of puerperium, malabsorption, gastric dystrophy, diet and infection in the aetiology of the disease. All 5 factors were found to be common, and to occur in a variety of combinations, producing a wide spectrum of illness variously resembling nutritional megaloblastic anaemia, sprue, pernicious anaemia and many stages in between. It is concluded that megaloblastic anaemia in this population is a multifactorial disease, and a tentative scheme, relating the aetiological factors, is drawn up. Neither serum vitamin B(12) levels, nor folate estimation in serum or red cells emerged as very reliable guides to the underlying biochemical deficiency.

Topics: Adolescent; Adult; Anemia, Macrocytic; Anemia, Megaloblastic; Clinical Trials as Topic; Double-Blind Method; Female; Folic Acid; Humans; Infections; Malabsorption Syndromes; Male; Tetracycline; Vitamin B 12

Investigations on 114 anaemic pregnant women revealed that megaloblastosis occurred in more than half. A therapeutic follow-up approach clearly indicated that vitamin B12-deficiency was fairly common in such patients; the need of iron supplementation in many of them for achieving complete remission emphasized the poor status of iron stores. All patients with normoblastic marrow achieved full remission with iron therapy alone. The deficiency of haematinic factors appears to be largely due to poor nutrition.

Topics: Anemia; Anemia, Megaloblastic; Female; Folic Acid; Hemoglobins; Humans; India; Iron; Pregnancy; Pregnancy Complications, Hematologic; Vitamin B 12

Fifty-three patients with megaloblastic anaemia treated with cyanocobalamin and folic acid have been studied. Repeat marrow examination was found to be of value in assessing response to treatment. The early improvement in marrow morphology in patients with pernicious anaemia was greater with 1000 mug than with 5 mug doses of cyanocobalamin. The effect of folate deficiency in delaying marrow response to cyanocobalamin in patients with pernicious anaemia is described and combined cyanocobalamin and folic acid treatment was found to be more effective than either alone. The response to large doses of cyanocobalamin in folate deficient patients was unrelated to the initial serum vitamin B12 level.

Topics: Adult; Aged; Anemia, Macrocytic; Anemia, Megaloblastic; Bone Marrow Examination; Clinical Trials as Topic; Erythroblasts; Erythrocytes; Female; Folic Acid; Folic Acid Deficiency; Humans; Iron; Male; Middle Aged; Time Factors; Vitamin B 12

Topics: Anemia, Megaloblastic; Humans; Malabsorption Syndromes; Proteinuria; Vitamin B 12; Vitamin B 12 Deficiency

The aim of this study was to investigate the subclinical involvement of the optic nerve in asymptomatic patients with vitamin B12 deficiency using visual evoked potentials.. This study included 40 asymptomatic patients diagnosed with vitamin B12 deficiency (considered as serum levels below 150 pg/mL) and a control group of 40 healthy individuals. All participants underwent a visual evoked potential examination. Routine screening for homocysteine was performed for patients with vitamin B12 deficiency. The levels of vitamin B12 and homocysteine and the presence of megaloblastic anemia were analyzed statistically compared with P100, N75, and N135 latencies and amplitudes.. The mean vitamin B12 level was 96 pg/mL in the patient group and 374 pg/mL in the control group. In the patient group, 24 (60%) patients had hyperhomocysteinemia and 8 (20%) patients had megaloblastic anemia. The P100 wave latency of patients with vitamin B12 deficiency was significantly prolonged compared with the control group ( P < 0.01). There was no significant difference in the P100 amplitude between the patient group and the control group. P100 latencies were significantly longer in patients with hyperhomocysteinemia ( P = 0.002).. Our study showed that patients with vitamin B12 deficiency may have visual evoked potential abnormalities without visual symptoms or examination findings. In addition, high homocysteine levels led to a prolonged P100 latency in the patient group independent of vitamin B12 levels.

Topics: Anemia, Megaloblastic; Evoked Potentials, Visual; Humans; Hyperhomocysteinemia; Vitamin B 12; Vitamin B 12 Deficiency

Anemia-causing fever has been described in patients with megaloblastic anemia. Although the exact mechanism of this is unknown, high-grade fever is relatively less reported.. This prospective observational study included all new cases of megaloblastic anemia presenting with febrile illness (>101°F) during a 3-year period. Patients with existing anemia, comorbidities, and other causes of macrocytosis were excluded. A detailed evaluation for megaloblastic anemia and workup for excluding tropical infections was done. The patients were treated with parenteral vitamin B12, folic acid, and other hematinics.. Around 24 cases of megaloblastic anemia presenting with high-grade fever were included, with 14 (58.3%) males, mean duration of fever 7.7 days (4-18 days), and 09 (37.5%) having temperature >103°F. The mean hemoglobin (Hb) was 8.15 g/dL (3.7-11.1 g/dL), the mean corpuscular volume (MCV) was 111 ± 7.8 fL, 18 (75%) had unconjugated hyperbilirubinemia, the mean lactate dehydrogenase (LDH) was 814 ± 24 IU/L, and 21 (87.5%) had low B12 or folate levels. Most showed good therapeutic response to B12 or folic acid with defervescence in 1-5 days (mean 2.6 days) and improvement in lab parameters in 1 week. The study population was divided into those with temperature ≥103°F, and temperature <103°F it was seen that there was a significant association (p < 0.05) with leucocyte count of ≤3000/cumm, and MCV ≥110 fL, in patients with temperature ≥103°F Conclusion: Megaloblastic anemia should be considered in the differentials of a patient presenting with a febrile illness with no clinical localization and a negative initial fever workup. Early identification and prompt therapy of this easily treatable disorder are very essential.

Topics: Anemia; Anemia, Megaloblastic; Female; Folic Acid; Folic Acid Deficiency; Humans; Male; Vitamin B 12; Vitamin B 12 Deficiency

Vitamin B12, or cobalamin deficiency, an infrequent clinical entity in pediatric age, is found almost solely in breastfed infants whose mothers are purely vegetarian, non-supplemented or with pernicious anemia. Megaloblastic anemia in infants presents with generalized weakness or irritability.. Diagnosis is usually centered on complete blood count, vitamin dosing, and peripheral smear, which may show macrocytes, hypersegmented neutrophils, reticulocytopenia and a raised mean corpuscular volume (MCV ˃ 100 fL). Pancytopenia has also been noted.. We report an exclusive breastfed nine-month-old female child who presented with irritability, developmental delay, and difficulties in introducing new foods. Her initial blood count revealed pancytopenia. Vitamin B12 levels were found to be reduced. Maternal levels of Vitamin B12 were also found to be borderline low. The child was treated as per protocols, and improvement was evidenced with the return of hematological parameters to the regular and gradual advancement of milestones.. We aim to underscore the importance of megaloblastic anemia as an important and rare cause of anemia in infancy.

Topics: Anemia, Megaloblastic; Anemia, Pernicious; Child; Female; Humans; Infant; Pancytopenia; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Megaloblastic; Humans; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins

In infants, vitamin B12 deficiency is mainly due to nutritional deficiencies related to maternal deficit. Most cases of maternal deficiencies are associated with vegetarian diets. Pernicious anemia is an au toimmune disease that affects the absorption of this vitamin. Although it is less common than nutri tional deficiency, is also an important cause of maternal deficiency.. to report a case of an infant with vitB12 deficiency, secondary to pernicious anemia in his mother, and to review the most important aspects of this disease in childhood.. Nine months-old male infant, without pathological perinatal history, exclusively breastfed, with persistent rejection of solid food from 6 months of age. One month before hospitalization, he progressively presented hyporesponsiveness, with fluctuating state of alertness, regression of motor development milestones, and vomiting. The blood count showed macrocytic anemia and neutropenia. Vitamin B12 deficiency was confirmed in the patient. He received treatment with intramuscular vitamin B12 with good clinical and laboratory response. Maternal B12 deficiency was confirmed as the cause of the infant's deficiency. Since the mother reported no dietary restrictions, anti-intrinsic factor and anti-parietal cell antibodies were measured, leading to the diagnosis of pernicious anemia.. Early recognition is essential to prevent the development of potentially irreversible neurological damage. Maternal pernicious ane mia should be considered in children with megaloblastic anemia, especially in those whose mothers do not follow vegetarian diets.

Topics: Anemia, Megaloblastic; Anemia, Pernicious; Child; Female; Humans; Infant; Male; Mothers; Pregnancy; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Megaloblastic; Humans; Nutrition Therapy; Vitamin B 12

Variation in vitamin B

Topics: Anemia, Megaloblastic; Anemia, Pernicious; Genome-Wide Association Study; Humans; Mendelian Randomization Analysis; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins

Imerslund-Gräsbeck syndrome is an autosomal recessive disorder of vitamin B12 malabsorption presenting with megaloblastic anemia and mild proteinuria in childhood. The disorder is caused by biallelic pathogenic variants in the CUBN or AMN genes, which encode proteins involved in B12 absorption. We present the case of a 17-month-old boy with failure to thrive, pancytopenia, and fevers. His megaloblastic anemia was overlooked leading to unnecessary invasive testing. Findings on bone marrow biopsy prompted investigation for genetic disorders of B12 metabolism. Exome sequencing uncovered 1 known pathogenic variant and 1 novel likely pathogenic variant in CUBN, confirming the diagnosis of Imerslund-Gräsbeck syndrome.

Topics: Anemia, Megaloblastic; Female; Humans; Infant; Malabsorption Syndromes; Male; Pancytopenia; Proteinuria; Vitamin B 12; Vitamin B 12 Deficiency

Vitamin B12 deficiency has been associated with a very wide spectrum of neurologic manifestations and the majority of cases occur in infants, pregnant women, and elderly people. In children, common neurological complications include neuropathy, neuropsychiatric features, infantile tremor syndrome, developmental delay, cognitive decline, spastic paraparesis due to subacute combined degeneration of cord, seizures, encephalopathy, extrapyramidal features, and neuropathy. Vitamin B12 is known to cause sensory ataxia, along with impaired position and vibration sense, as well as variable spasticity, as a part of subacute combined degeneration of the spinal cord. However, only a few cases of isolated cerebellar ataxia caused by vitamin B12 deficiency have been reported in published literature.. We are reporting a case of isolated cerebellar ataxia progressing over months in a 13-year-old boy. He also had associated knuckle hyperpigmentation, megaloblastic anemia and his magnetic resonance imaging of the brain was normal. Complete blood count showed hemoglobin of 8.6 gm/dl and peripheral smear showed macrovalocytes and few hypersegmented neutrophils. Serum vitamin B12 level was low (134 pg/mL). He was started on daily intramuscular vitamin B12 supplementation and he showed a favorable response after the first week.. Clinicians need to consider vitamin B12 deficiency as one of the rare etiological possibilities in children presenting with isolated subacute onset/chronic ataxia, as supplementation of this vitamin is likely to cause a complete reversal of ataxia in such children.

Topics: Aged; Anemia, Megaloblastic; Brain; Child; Female; Humans; Infant; Magnetic Resonance Imaging; Male; Pregnancy; Vitamin B 12; Vitamin B 12 Deficiency

The clinical data of two children with Imerslund-Gräsbeck syndrome (IGS) who were admitted to the First Affiliated Hospital of Zhengzhou University in August 2019 was analyzed retrospectively. The two cases were siblings, aged 8 years and 8 months and 6 years and 2 months, respectively. These two boys had megaloblastic anemia, low level of vitamin B. 回顾分析郑州大学第一附属医院2019年8月收治的两例Imerslund-Gräsbeck综合征（IGS）患儿的临床资料。两例患儿为同胞兄弟，年龄分别为8岁8个月和6岁2个月，检查均示巨幼红细胞性贫血，血清维生素B

Topics: Anemia, Megaloblastic; Child; Humans; Malabsorption Syndromes; Male; Proteinuria; Retrospective Studies; Siblings; Vitamin B 12; Vitamin B 12 Deficiency

Vitamin B12 deficiency in children can cause megaloblastic anemia, poor growth, and increased chances of infections. It is an important reversible cause of bone marrow suppression which at the time of presentation can mimic hematological malignancy. Therefore, it should be considered as a differential diagnosis in cases suspected of acute leukemia. We report a case of 14 months old child who had atypical presentation of vitamin B12 deficiency. He had chronic fever, decreased feeding and increased paleness for one year. Pancytopenia with severe anemia was present along with 19% reactive/atypical cells in peripheral blood smear suggesting acute leukemia. However, bone marrow aspiration and biopsy showed features of megaloblastic anemia. Vitamin B12 level measured was very low and treatment with cyanocobalamin caused drastic improvement in the child's condition.

Topics: Anemia, Megaloblastic; Humans; Infant; Leukemia; Male; Pancytopenia; Vitamin B 12; Vitamin B 12 Deficiency

Imerslund-Gräsbeck syndrome is an autosomal recessive disease reported only in certain pure-breed dogs. An 18-month-old, male neutered beagle cross-breed was presented for evaluation of severe lethargy, progressive weakness and anorexia. Main clinicopathological findings included low body condition score (2.5/9), severe muscle atrophy, several neurological abnormalities, mild normochromic, normocytic, non-regenerative anaemia, severe hypocobalaminemia and mild proteinuria. Extensive diagnostic tests ruled out most of differential diagnoses for the aforementioned clinicopathological abnormalities and genetic evaluation showed that the dog was heterozygous for two previously described mutations affecting the CUBN gene, the beagle and the border collie variants. The dog showed an excellent clinical response to oral cobalamin supplementation with no relapse after 4 months. In conclusion, this case creates awareness that Imerslund-Gräsbeck syndrome should be considered even in mixed-breed dogs with compatible clinical signs and that two different pathogenic CUBN mutations in compound heterozygosity can lead to a typical Imerslund-Gräsbeck syndrome phenotype.

Topics: Anemia, Megaloblastic; Animals; Dog Diseases; Dogs; Malabsorption Syndromes; Male; Proteinuria; Vitamin B 12; Vitamin B 12 Deficiency

Imerslund-Gräsbeck syndrome is a rare genetic disease characterised by vitamin B. A 4-year old Sri Lankan boy presented with gradually worsening difficulty in walking for two weeks duration. He was previously diagnosed and managed as having non-transfusion-dependent α-thalassaemia based on the presence of hypochromic microcytic anaemia, haemoglobin H inclusion bodies in the blood film and compound heterozygous α-thalassaemia genotype with a gene deletion. However, his transfusion requirement increased over the past three months and he gradually lost his motor developmental milestones during two weeks before admission. The neurological examination revealed generalised hypotonia, exaggerated knee jerks and extensor plantar response. His complete blood count showed pancytopenia, and bone marrow biopsy revealed megaloblastic changes. Serum vitamin B. This case report presents a rare occurrence of severe vitamin B

Topics: alpha-Thalassemia; Anemia, Megaloblastic; Child; Child, Preschool; Humans; Malabsorption Syndromes; Male; Proteinuria; Subacute Combined Degeneration; Vitamin B 12; Vitamin B 12 Deficiency

Imerslund-Gräsbeck syndrome (IGS) is a rare autosomal-recessive disorder characterized by selective vitamin B12 malabsorption, megaloblastic anemia, and proteinuria. The precise incidence of this disorder is unknown in the Middle East and Arab countries. The disease is caused by a homozygous variant in either AMN or CUBN genes. In addition, some compound heterozygous variants are reported.. Clinical and laboratory data of patients diagnosed with IGS in Oman were retrospectively collected. Mutation analysis for all genes involved in vitamin B12/folic acid metabolism and megaloblastic anemia was conducted using next-generation sequencing (NGS).. Three siblings (2 girls and a boy) have been diagnosed with the condition. They exhibit a phenotypic variability with different age of presentation and different spectrum of disease. All patients harbor a novel biallelic frameshift mutation in exon 11 of AMN gene (p.Pro409Glyfs*), which was not reported previously in the literature. Both parents are heterozygotes for the same variant. All patients responded well to vitamin B12 parenteral therapy, but proteinuria persisted.. In communities with high incidence of consanguinity, cases of early-onset vitamin B12 deficiency should be thoroughly investigated to explore the possibility of Imerslund-Gräsbeck syndrome and other vitamin B12-related hereditary disorders. Further local and regional studies are highly recommended.

Topics: Anemia, Megaloblastic; Child; Child, Preschool; Exons; Female; Frameshift Mutation; Humans; Infant; Malabsorption Syndromes; Male; Membrane Proteins; Proteinuria; Retrospective Studies; Siblings; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex

Topics: Aged; Anemia, Megaloblastic; Anemia, Pernicious; Folic Acid; Homocysteine; Humans; Injections, Intramuscular; Male; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency

A 62-year-old Japanese woman developed numbness of the extremities and megaloblastic anemia. She had undergone total abdominal hysterectomy, whole-pelvis radiation therapy and chemotherapy for gynecological cancer 10 years before. Chronic abdominal pain, diarrhea and intermittent small-bowel obstruction had afflicted her for a long time. We diagnosed her with vitamin B12 deficiency anemia and polyneuropathy due to chronic radiation enteritis causing malabsorption. Vitamin B12 injections improved her numbness and anemia. The early diagnosis and treatment of deficiency of vitamin B12 are important. Physicians should regularly measure vitamin B12 levels and supplement vitamin B12 as needed in patients with chronic radiation enteritis.

Topics: Anemia, Megaloblastic; Enteritis; Female; Gastrointestinal Diseases; Genital Neoplasms, Female; Humans; Hypesthesia; Malabsorption Syndromes; Middle Aged; Polyneuropathies; Radiation Injuries; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Megaloblastic; Humans; Neural Conduction; Neurologic Examination; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adolescent; Anemia, Megaloblastic; Cells, Cultured; Clone Cells; CRISPR-Cas Systems; Exome Sequencing; Folic Acid; Frameshift Mutation; Gene Knockout Techniques; Homozygote; Humans; Hyperhomocysteinemia; K562 Cells; Male; Recurrence; Sequence Deletion; Sodium-Hydrogen Exchanger 1; Vitamin B 12

Megaloblastic anaemia due to vitamin B12 and folic acid deficiency is uncommon in infancy and rarely reported in infants below 3 months of age. We hereby report a case of megaloblastic anaemia in a 9-weeks old infant having fever from 7th week of life. Blood picture showed pancytopenia and diagnosis was confirmed on bone marrow biopsy and serum level of vitamins. Patient positively responded to vitamin B12 and folic acid supplementation. Infants with pancytopenia even younger than 2 months, should also be investigated for vitamin B12 and folate deficiency. Mother of the baby was not antenatally investigated for anaemia. Prompt antenatal diagnosis and treatment of mothers can reduce the incidence in the infants.

Topics: Anemia, Megaloblastic; Bone Marrow; Diagnosis, Differential; Early Diagnosis; Early Medical Intervention; Failure to Thrive; Folic Acid; Folic Acid Deficiency; Humans; Infant; Male; Pancytopenia; Prenatal Care; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins

Topics: Anemia, Megaloblastic; Breast Feeding; Female; Humans; Infant; Male; Maternal Nutritional Physiological Phenomena; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex

Topics: Anemia, Megaloblastic; Blood Cells; Blood Transfusion; Child, Preschool; Female; Hemoglobins; Homozygote; Humans; Malabsorption Syndromes; Membrane Proteins; Mutation; Proteinuria; Vitamin B 12; Vitamin B 12 Deficiency

Transcobalamin (TC) transports vitamin B12 from blood into cells. TC II deficiency is a rare autosomal recessive disorder. It is characterized by failure to thrive, diarrhoea, pallor, anaemia, pancytopenia or agammaglobulinemia. It is usually confirmed by molecular analysis of the TCN2 gene. We report a 2-month-old girl with two novel mutations, which were first reported in humans.. We present a 2-month-old Chinese girl with pancytopenia, severe combined immunodeficiency disease, and megaloblastic anaemia. Targeted next-generation sequencing (NGS) was performed, which detected compound heterozygous variants in exon 7 of the TCN2 gene (Mutation 1: c.1033 C > T; Mutation 2: c.1017-1031delinsGTAACAGAGATGGTT). These mutations result in stop codons in TCN2. The c.1033C > T mutation causes a stop at codon 345 (p.Gln345Ter), and the c.1017-1031delinsGTAACAGAGATGGTT mutation causes a stop at codon 340 (p.Leu340Ter). After being diagnosed, she was treated with intramuscular 1 mg hydroxycobalamin (OH-Cbl) every day for 2 months. The CBC value returned to normal after half a month. The peripheral blood lymphocyte subsets and immunoglobulin recovered after 2 months. Then, the dosage of OH-Cbl was gradually reduced.. TC II deficiency is a serious complication that requires lifelong treatment. Its diagnosis is difficult due to the lack of clearly identifiable symptoms. Genetic testing should be performed as early as possible if this disease is suspected. The specific observations of this case report make a considerable contribution to the literature and provide a reference for the diagnosis and treatment of future cases.

Topics: Anemia, Megaloblastic; China; Female; Humans; Infant; Mutation; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Hemolytic; Anemia, Megaloblastic; Folic Acid; Humans; Purpura, Thrombotic Thrombocytopenic; Vitamin B 12

Topics: Anemia, Megaloblastic; Blood Cells; Child; Female; Homocystinuria; Humans; India; Male; Vitamin B 12

A combination of anaemia and knuckle pigmentation should always raise concern for megaloblastic anaemia. As the terminal ileum is the site of vitamin B

Topics: Adolescent; Anemia, Megaloblastic; Antitubercular Agents; Drug Therapy, Combination; Humans; Ileum; Male; Treatment Outcome; Tuberculin Test; Tuberculosis, Gastrointestinal; Vitamin B 12; Vitamin B 12 Deficiency

Efficacy of PO cobalamin (Cbl) supplementation in dogs with hereditary Cbl malabsorption (Imerslund-Gräsbeck syndrome, IGS) is unknown.. To evaluate PO Cbl supplementation in Beagles with IGS previously treated parenterally. We hypothesized that 1 mg cyano-Cbl daily PO would maintain clinical and metabolic remission.. Three client-owned Beagles with IGS and 48 healthy control dogs.. Prospective study. Daily PO cyanocobalamin (cyano-Cbl; 1 mg) supplementation was monitored for 13 (2 dogs) and 8 months (1 dog). Health status was assessed by owner observations. Methylmalonic acid (MMA)-to-creatinine concentrations were measured using an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-TMS) method on urine samples collected monthly. Concurrent measurements of serum MMA concentration (n = 7; UPLC-TMS) were available for 1 dog.. All dogs remained in excellent health during PO supplementation. Urine MMA remained consistently low in 2 dogs (median, 2.5 mmol/mol creatinine; range, 1.2-9; healthy dogs [n = 30], median, 2.9 mmol/mol creatinine; range, 1.3-76.5). Urine MMA ranged from 38.9-84.9 mmol/mol creatinine during the first 6 months in 1 dog already known to excrete comparable amounts when supplemented parenterally. Brief antibiotic treatment for an unrelated condition after 6 months resulted in low urine MMA (median, 2.8 mmol/mol creatinine; range, 1.9-4.8) for the next 7 months. All concurrent serum MMA concentrations (median, 651 nmol/L; range, 399-919) before and after month 6 were within the established reference interval (393-1476 nmol/L; n = 48).. One milligram of cyano-Cbl daily PO appears efficacious for maintaining normal clinical status and normal cellular markers of Cbl metabolism in Beagles with IGS.

Topics: Administration, Oral; Anemia, Megaloblastic; Animals; Dog Diseases; Dogs; Female; Malabsorption Syndromes; Male; Methylmalonic Acid; Proteinuria; Vitamin B 12; Vitamin B 12 Deficiency

Imerslund-Gräsbeck syndrome (IGS) is a rare autosomal recessive disorder clinically characterized by megaloblastic anemia, benign mild proteinuria, and other nonspecific symptoms. Several pathogenetic variants in the amnionless (

Topics: Anemia, Megaloblastic; Female; Genetic Variation; Humans; Infant; Infusions, Parenteral; Introns; Malabsorption Syndromes; Membrane Proteins; Proteins; Proteinuria; RNA Splicing; Sequence Analysis, DNA; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Megaloblastic; Breast Neoplasms; Folic Acid; Folic Acid Deficiency; Humans; Retrospective Studies; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Administration, Oral; Adult; Anemia, Megaloblastic; Female; Humans; India; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Megaloblastic; Diet, Vegan; Dietary Supplements; Female; Humans; Middle Aged; Neglected Diseases; Psychotic Disorders; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency

Normal red blood cells maturation depends on many different hematological factors, including vitamin (vit.) B12. Megaloblastic anemias are basically caused by vit. B12 deficiency. In childhood the deficiency of this vitamin is extremely rare. The article captures findings of observation of the patient with rare form congenital vit. B12 deficiency anemia - Imerslund-Gräsbeck syndrome. The disease is characterized with selective intestinal malabsorption of vit. B12 and permanent proteinuria, without sings of kidney disease. The diagnosis was confirmed by our team in early childhood and based on the history, clinical and paraclinical data. After two weeks of specific treatment with vit. B12 , complete clinical - hematological remission was achieved. Treatment includes lifelong vit. B12 injections once per month. Cathamnesic observation for 18 months revealed that the patient is in remission, but there was continued macrocytosis of red blood cells and mild proteinuria. The presented case is interesting as a rare case of megaloblastic anemia caused by vit. B12 deficiency in childhood. Such patients often treated under different diagnosis. In such cases early diagnosis, treatment and prevention are crucial for the good prognosis.

Topics: Anemia, Megaloblastic; Child; Child, Preschool; Humans; Malabsorption Syndromes; Proteinuria; Rare Diseases; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency

An 11-month-old Border collie presented collapsed and continued to deteriorate rapidly despite supportive treatment. The dog had a history of failure to thrive and recurring respiratory infection. Laboratory abnormalities included neutrophilic leucocytosis, Heinz body anaemia, hyperammonaemia, hyperbilirubinaemia, proteinuria and hypocobalaminaemia. Post-mortem examination revealed multi-focal necrosis within the heart, kidneys, pancreas, liver, meninges and cerebral cortex. Fungal hyphae in lesions were identified as Scedosporium prolificans following culture. Subsequent genotyping confirmed that the dog carried the CUBN:c.8392delC mutation in a homozygous state, verifying hereditary cobalamin deficiency (a.k.a. Imerslund-Gräsbeck syndrome). Cobalamin deficiency may have been a predisposing factor for the development of systemic fungal infection in this dog.

Topics: Anemia, Megaloblastic; Animals; Dog Diseases; Dogs; Malabsorption Syndromes; Male; Mycoses; Proteinuria; Scedosporium; Vitamin B 12; Vitamin B 12 Deficiency

Vitamin B

Topics: Adolescent; Anemia, Megaloblastic; Diet, Vegetarian; Directive Counseling; Female; Humans; Injections, Intramuscular; Jaundice; Patient Compliance; Patient Education as Topic; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency

Prospective studies on maintenance treatment for Beagles with hereditary selective cobalamin (Cbl) malabsorption (Imerslund-Gräsbeck syndrome, IGS) are lacking. In our experience, measurement of methylmalonic acid (MMA), a Cbl-dependent metabolite, seems more helpful to monitor Cbl status as compared with serum Cbl concentrations.. To evaluate a standardized Cbl supplementation scheme in Beagles with IGS. We hypothesized that a single parenteral dose of 1 mg hydroxocobalamin (OH-Cbl) would maintain clinical and metabolic remission for up to 2 months.. Six client-owned juvenile Beagles with genetically confirmed IGS and 28 healthy control dogs.. Prospective study. Monthly IM OH-Cbl (1 mg) supplementation was done over a median of 9 months (range, 6-13) in 6 dogs, followed by bimonthly (every 2 months) injections in 5 dogs over a median of 6 months (range, 3-10). Health status was assessed by routine clinical examinations at injection time points and owner observations. Voided urine samples were collected immediately before OH-Cbl injections for measurement of MMA-to-creatinine concentrations using a gas-liquid chromatography-tandem mass spectrometry (GC-MS) method.. All dogs were clinically healthy while receiving monthly and bimonthly OH-Cbl supplementation. Urinary MMA results in healthy dogs ranged from 1.3 to 76.5 mmol/mol creatinine (median, 2.9). Median urinary MMA concentrations did not differ between dogs with IGS receiving monthly (n = 49; 5.3 mmol/mol creatinine; range, 2.3-50.4) and bimonthly (n = 31; 5.3 mmol/mol creatinine; range, 1.6-50) injections.. A maintenance parenteral dose of 1 mg OH-Cbl monthly or bimonthly appears adequate in Beagles with IGS monitored by metabolic testing.

Topics: Anemia, Megaloblastic; Animals; Creatinine; Dog Diseases; Dogs; Drug Administration Schedule; Female; Hydroxocobalamin; Injections, Intramuscular; Malabsorption Syndromes; Male; Methylmalonic Acid; Prospective Studies; Proteinuria; Vitamin B 12; Vitamin B 12 Deficiency

The endocytic receptor cubam formed by the 460-kDa protein cubilin and the 45-kDa transmembrane protein amnionless (AMN), is essential for intestinal vitamin B

Topics: Albumins; Amino Acid Sequence; Anemia, Megaloblastic; Animals; CHO Cells; Cricetulus; Crystallography, X-Ray; Humans; Intestinal Mucosa; Kidney; Malabsorption Syndromes; Membrane Proteins; Mutation; Protein Binding; Protein Conformation; Proteins; Proteinuria; Receptors, Cell Surface; Sequence Homology, Amino Acid; Vitamin B 12; Vitamin B 12 Deficiency

Three Komondor dogs in a small family and 3 sporadic cases exhibited a constellation of signs that included juvenile-onset of failure-to-thrive, inappetence, vomiting and/or diarrhea, and weakness. In each we documented dyshematopoiesis, increased anion gap, methylmalonic acidemia/-uria, and serum cobalamin deficiency. Urine protein electrophoresis demonstrated excretion of cubam ligands. All clinical signs and metabolic abnormalities, except proteinuria, were reversed by regular parenteral cobalamin administration. The pattern of occurrence and findings in the disorder suggested an autosomal recessive inheritance of cobalamin malabsorption with proteinuria, a condition in humans called Imerslund-Gräsbeck syndrome. The purpose of this study was to determine the molecular cause of this disorder in Komondors.. Whole genome sequencing of two affected Komondor dogs of unknown relatedness and one parent and a clinically-normal littermate of an affected dog revealed a pathogenic single-base change in the CUBN intron 55 splice donor consensus sequence (NM_001003148.1: c.8746 + 1G > A) that was homozygous in affected dogs and heterozygous in the unaffected parents. Alleles of the variant co-segregated with alleles of the disease locus in the entire family and all more distantly-related sporadic cases. A population study using a simple allele-specific DNA test indicated mutant allele frequencies of 8.3 and 4.5% among North American and Hungarian Komondors, respectively.. DNA testing can be used diagnostically in Komondors when clinical signs are suggestive of cobalamin deficiency or to inform Komondor breeders prospectively and prevent occurrence of future affected dogs. This represents the third cubilin variant causing inherited selective cobalamin malabsorption in a large animal ortholog of human Imerslund-Gräsbeck syndrome.

Topics: Anemia, Megaloblastic; Animals; Breeding; Dog Diseases; Dogs; Female; Genotype; Malabsorption Syndromes; Male; Protein Isoforms; Proteinuria; Receptors, Cell Surface; United States; Vitamin B 12; Vitamin B 12 Deficiency; Whole Genome Sequencing

Black cohosh rhizome, available as a dietary supplement, is most commonly marketed as a remedy for dysmenorrhea and menopausal symptoms. A previous subchronic toxicity study of black cohosh dried ethanolic extract (BCE) in female mice revealed a dose-dependent ineffective erythropoiesis with a macrocytosis consistent with the condition known as megaloblastic anemia. The purpose of this study was to investigate potential mechanisms by which BCE induces these particular hematological changes. B6C3F1/N female mice (32/group) were exposed by gavage to vehicle or 1,000 mg/kg BCE for 92 days. Blood samples were analyzed for hematology, renal and hepatic clinical chemistry, serum folate and cobalamin, red blood cell (RBC) folate, and plasma homocysteine and methylmalonic acid (MMA). Folate levels were measured in liver and kidney. Hematological changes included decreased RBC count; increased mean corpuscular volume; and decreased reticulocyte, white blood cell, neutrophil, and lymphocyte counts. Blood smear evaluation revealed increased Howell-Jolly bodies and occasional basophilic stippling in treated animals. Plasma homocysteine and MMA concentrations were increased in treated animals. Under the conditions of our study, BCE administration caused hematological and clinical chemistry changes consistent with a functional cobalamin, and possibly folate, deficiency. Further studies are needed to elucidate the mechanism by which BCE causes increases in homocysteine and MMA.

Topics: Anemia, Megaloblastic; Animals; Body Weight; Cimicifuga; Female; Folic Acid; Homocysteine; Kidney; Liver; Methylmalonic Acid; Mice; Plant Extracts; Tetrahydrofolate Dehydrogenase; Vitamin B 12; Vitamin B 12 Deficiency

The association between obesity and different types of anemia remained uncertain. The present study aimed to assess the relation between obesity parameters and the occurrence of iron deficiency anemia and also megaloblastic anemia among Iranian population.. This cross-sectional study was performed on 1252 patients with morbid obesity that randomly selected from all patients referred to Clinic of obesity at Rasoul-e-Akram Hospital in 2014. The morbid obesity was defined according to the guideline as body mass index (BMI) equal to or higher than 40 kg/m2. Various laboratory parameters including serum levels of hemoglobin, iron, ferritin, folic acid, and vitamin B12 were assessed using the standard laboratory techniques.. BMI was adversely associated with serum vitamin B12, but not associated with other hematologic parameters. The overall prevalence of iron deficiency anemia was 9.8%. The prevalence of iron deficiency anemia was independent to patients' age and also to body mass index. The prevalence of vitamin B12 deficiency was totally 20.9%. According to the multivariable logistic regression model, no association was revealed between BMI and the occurrence of iron deficiency anemia adjusting gender and age. A similar regression model showed that higher BMI could predict occurrence of vitamin B12 deficiency in morbid obese patients.. Although iron deficiency is a common finding among obese patients, vitamin B12 deficiency is more frequent so about one-fifth of these patients suffer vitamin B12 deficiency. In fact, the exacerbation of obesity can result in exacerbation of vitamin B12 deficiency.

Topics: Adolescent; Adult; Aged; Anemia, Iron-Deficiency; Anemia, Megaloblastic; Biomarkers; Body Mass Index; Child; Cross-Sectional Studies; Female; Ferritins; Folic Acid; Hemoglobins; Hospitals, University; Humans; Iran; Iron; Male; Middle Aged; Obesity, Morbid; Prevalence; Vitamin B 12; Vitamin B Complex

Inborn errors of cobalamin (Cbl) metabolism form a large group of rare diseases. One of these, Cbl deficiency type C (CblC), is a well-known cause of thrombotic microangiopathy (TMA), especially in infants. However, there has only been a single published case of TMA associated to Cbl deficiency type G (CblG), also known as methionine synthase deficiency (MSD).. A 21-month-old boy presented with pallor and oral ulcers during episodes of upper respiratory infection (URI). Further examination revealed signs of TMA, and the patient progressed to acute renal failure (ARF). Renal biopsy showed TMA. Evaluation for infection and autoantibodies were negative. The C3 and C4 complement fractions were normal. Analysis of the bone marrow aspirate suggested megaloblastic anemia and signs of hematopoiesis activation (secondary to peripheral hemolysis). Although the serum vitamin B12 level was normal, the patient was treated with cyanocobalamin, with no improvement. The ARF and hematologic parameters improved with conservative treatment. A severe relapse occurred during the follow-up, with normal ADAMTS13 activity. The presumed diagnosis was atypical hemolytic uremic syndrome, and the patient was started on eculizumab, but his response was poor, even when the dosage was increased. At this point it was also recognized that his developmental speech was delayed. Based on these findings, whole exome sequencing was performed, leading to the detection of two novel deleterious variants in the gene coding for methionine synthase, confirming the diagnosis of MSD. Subsequent treatment consisted of elevating the patient's serum homocysteine level and starting him on hydroxicobalamin, with normalization of all hematologic parameters although the microalbuminuria remained.. Methionine synthase deficiency is very rare and characterized by megaloblastic anemia and neurological symptoms. We report the second case of MSD associated to TMA previously diagnosed as aHUS in which the patient had a poor response to eculizumab.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Acute Kidney Injury; ADAMTS13 Protein; Anemia, Megaloblastic; Antibodies, Monoclonal, Humanized; Atypical Hemolytic Uremic Syndrome; Biopsy; Bone Marrow; Exome Sequencing; Humans; Hydroxocobalamin; Hyperhomocysteinemia; Infant; Kidney; Language Development Disorders; Male; Metabolism, Inborn Errors; Recurrence; Thrombotic Microangiopathies; Vitamin B 12; Vitamin B Complex

Topics: Anemia, Megaloblastic; Blood Transfusion; Child; Humans; Transfusion Reaction; Tremor; Vitamin B 12

Topics: Anemia, Megaloblastic; Folic Acid; Humans; Vitamin B 12

Topics: Anemia, Megaloblastic; Folic Acid; Humans; Vitamin B 12

Topics: Anemia, Megaloblastic; Folic Acid; Humans; Vitamin B 12

We report a case of a 17-year-old female patient who presented with sudden, painless, nonprogressive diminished vision in both eyes (best corrected visual acuity in right eye - 6/60 and left eye - 6/36). An ophthalmological evaluation revealed bilateral pale tarsal conjunctiva and bilateral macular hemorrhage. Hematological evaluation revealed the presence of megalocytic anemia (with hemoglobin - 4.9 g%). General examination showed severe pallor. On systemic examination, no abnormality was detected, confirmed by ultrasonography abdomen. Other causes of severe anemia have been ruled out. Intraocular pressure in both eyes was 12 mmHg. This case documents the rare occurrence of bilateral subinternal limiting membrane macular hemorrhage with megaloblastic anemia without thrombocytopenia and other retinal features of anemic retinopathy.

Topics: Adolescent; Anemia, Megaloblastic; Blood Transfusion; Combined Modality Therapy; Female; Folic Acid; Humans; Retinal Hemorrhage; Vision Disorders; Visual Acuity; Vitamin B 12

Over the last forty years, our laboratory has accumulated a collection of over 1000 cultured fibroblast lines derived from patients from around the world referred with signs of inborn errors of cobalamin or folate metabolism, including several hundred with complementation-confirmed diagnoses. By accurately classifying patient disorders into classes representing blocks affecting specific reactions, we have provide the basis for rational assessment of phenotypic heterogeneity, and development of methods for diagnosis, treatment and prognosis. These resources have been valuable in identification of causal genes for known inborn errors. Since 2000, we and our collaborators identified the genes for the cblA (MMAA), cblB (MMAB), cblC (MMACHC), cblD (MMADHC), and cblF (LMBRD1) disorders.. Whole exome sequencing of DNA from a patient with severe combined immunodeficiency (SCID), megaloblastic anemia and hemolytic uremic syndrome identified mutations in the MTHFD1 gene, which encodes a trifunctional enzyme involved in interconversion of folate coenzyme derivatives. This disorder demonstrates the importance de novo pyrimidine synthesis in the etiology of SCID. Mutations in the ABCD4 gene have been identified in four patients with accumulation of unbound cobalamin in lysosomes; this gene encodes a lysosomal membrane protein that plays a role in the transport of cobalamin across this membrane. Mutations in the HCFC1 gene on the X chromosome have been identified in several male patients that had received a diagnosis of cblC on the basis of complementation studies in cultured fibroblasts. HCFC1 encodes a transcription factor that regulates expression of a number of genes, including MMACHC, the gene that is mutated in patients with the cblC disorder. These studies demonstrate that with the advent of affordable whole exome sequencing, it has been possible to identify genes for novel inborn errors of cobalamin metabolism, often working from a small number of affected patients.

Topics: Anemia, Megaloblastic; ATP-Binding Cassette Transporters; Exome; Female; Folic Acid; Hemolytic-Uremic Syndrome; Host Cell Factor C1; Humans; Male; Methylenetetrahydrofolate Dehydrogenase (NADP); Minor Histocompatibility Antigens; Proto-Oncogene Proteins c-cbl; Severe Combined Immunodeficiency; Vitamin B 12

Megaloblastic anemia (MBA), also known as macrocytic anemia, is a type of anemia characterized by decreased number of RBCs as well as the presence of unusually large, abnormal and poorly developed erythrocytes (megaloblasts), which fail to enter blood circulation due to their larger size. Lack of vitamin-B12 (VB12) and / or folate (Vitamin-B9, VB9) with elevated homocysteine is the key factor responsible for megaloblastic anemia. Prior studies have demonstrated the induction of apoptosis in these abnormal under-developed erythrocytes. However, it is not clear whether this apoptosis induction is due to elevated p53 level or due to any other mechanism. Furthermore, it is also not fully known whether decreased vitamin-B12 and / or folate are responsible for apoptosis induction mediated by p53 in pre-erythroblasts.. Levels of serum VB9, VB12 and homocysteine in 50 patients suffering from MBA were compared with 50 non-megaloblastic anemia control subjects, who were referred by the clinicians for bone marrow examination for medical conditions other than MBA. Next, we have measured the p53 expression in the paraffin embedded blocks prepared from bone marrow biopsy, using immunohistochemistry, and the expression levels correlated with VB9 and VB12 levels.. Out of 50 MBA patients 40 (80%) and 44 (88%) subjects had very low VB12 and VB9 levels respectively. In contrast, only 2 (4%) and 12 (24%) non-megaloblastic anemia controls, out of 50 subjects, had low VB12 and VB9 respectively. Correlating with low vitamin B9 and B12, the homocysteine levels were high in 80% cases. But, only 20% non-megaloblastic controls exhibited high homocysteine in plasma. Immunohistochemical analysis for p53 expression showed a significantly high level of expression in MBA cases and no-or very low-expression in control subjects. Our correlation studies comparing the VB12 and VB9 levels with p53 expression concludes unusually high p53 levels in patients suffering from VB12 and VB9 deficiency induced MBA compared to control subjects not suffering from MBA.. Tumor protein p53 is the key protein expressed heavily in the bone marrow biopsies of patients suffering from VB12 and VB9 deficiency induced MBA but not in control subjects. Hence, p53 expression could be used as a surrogate marker for confirming the VB9 and VB12 induced MBA.

Topics: Aged; Aged, 80 and over; Anemia, Megaloblastic; Bone Marrow Examination; Female; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Male; Middle Aged; Tumor Suppressor Protein p53; Up-Regulation; Vitamin B 12; Vitamin B 12 Deficiency

Hepatitis B virus (HBV) typically causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma. It is associated with a variety of extrahepatic complications. We herein, present a rare extrahepatic complication of HBV infection. A 32-year man presented with melena, bleeding from gums and fever. Peripheral blood examination revealed anemia, macrocytosis and severe thrombocytopenia. His hepatitis B surface antigen (HBsAg) was positive but deoxyribonucleic acid (HBV DNA) by polymerase chain reaction (PCR) was negative. Other hepatitis, human immune deficiency virus (HIV), dengue, and autoimmune serology were negative. Bone marrow examination revealed megaloblastic erythropoiesis. There was mild to moderate reduction of megakaryocytes in bone marrow, which was not compatible with severe peripheral thrombocytopenia. His response to cyanocobalamin and folic acid was remarkable for myeloid cell lines and moderate for erythroid cell lines, but poor to platelet counts. Platelet counts gradually improved to safe limits with eltrombopag, likely reflecting autoimmune pathogenesis for thrombocytopenia. This case report highlights multiple targets of HBV infection with associated multiple pathogenetic mechanisms.

Topics: Adult; Anemia, Megaloblastic; Benzoates; Folic Acid; Folic Acid Deficiency; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B virus; Humans; Hydrazines; Male; Platelet Count; Polymerase Chain Reaction; Pyrazoles; Tenofovir; Thrombocytopenia; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex

Transcobalamin II deficiency is one of the rare causes of inherited vitamin B12 disorders in which the patients have characteristically normal or high vitamin B12 levels related to the transport defect of vitamin B12 into the cell, ending up with intracellular cobalamin depletion and high homocysteine and methylmalonic acid levels.. Herein, we describe the findings at presentation of four patients who were diagnosed to have transcobalamin II deficiency with novel mutations.. These patients with transcobalamin II deficiency were found to have novel mutations, of whom 2 had the same large deletion (homozygous c.1106+1516-1222+1231del).. Transcobalamin II deficiency should be considered in differential diagnosis of any infant with pancytopenia, failure to thrive, diarrhea, and vomiting.. Amaç: Transkobalamin II eksikliği nadir bir kalıtsal B12 vitamini bozukluğudur. Defektin B12 vitamininin transportu ile ilgili olması nedeniyle hastalar normal ya da yüksek B12 vitamini düzeylerine eşlik eden yüksek homosistein ve metilmalonik asit düzeylerine sahiptir. Gereç ve Yöntemler: Bu çalışmada transkobalamin II eksikliği tanısı alan dört hasta sunulmuştur. Bu hastalarda daha önce bildirilmemiş yeni mutasyonlar saptanmıştır. Bulgular: Hastaların ikisinde aynı büyük delesyon olduğu görülmüştür (homozigot c.1106+1516-1222+1231del). Sonuç: Pansitopeni, büyüme geriliği, ishal ya da kusması olan tüm bebeklerde transcobalamin II eksikliği ayırıcı tanıda düşünülmelidir.

Topics: Anemia, Megaloblastic; beta-Thalassemia; Bone Marrow; Chromosomes, Human, Pair 22; Codon, Nonsense; Consanguinity; Failure to Thrive; Female; Folic Acid; Frameshift Mutation; Genotype; Humans; Hydroxocobalamin; Infant; Male; Mutation; Mutation, Missense; Pancytopenia; Sequence Deletion; Transcobalamins; Vitamin B 12; Vomiting

Topics: Adult; Anemia, Megaloblastic; Delayed Diagnosis; Diabetes Mellitus, Type 2; Diagnosis, Differential; Female; Gout; Humans; Hypertension; Lichen Planus; Melanosis; Nail Diseases; Remission Induction; Vitamin B 12; Vitamin B 12 Deficiency

Premacular retrohyaloid hemorrhage is a rare complication of acute severe anemia. The authors report two cases of premacular hemorrhage in which no treatment other than clinical and spectral-domain optical coherence tomography observation was performed. The natural history of this condition reveals that complete clinical resolution is not accompanied by full anatomical restoration. [Ophthalmic Surg Lasers Imaging Retina. 2014;45:E5-E7.].

Topics: Acute Disease; Adult; Anemia, Hemolytic, Autoimmune; Anemia, Megaloblastic; Blood Transfusion; Fluorescein Angiography; Folic Acid; Folic Acid Deficiency; Glucocorticoids; Humans; Male; Retinal Hemorrhage; Thrombocytopenia; Tomography, Optical Coherence; Vision Disorders; Visual Acuity; Vitamin B 12; Vitamin B 12 Deficiency

Recent studies have focussed on the association between elevated homocysteine levels with megaloblastic changes and thromboembolic events, but the relationship between occult megaloblastosis (with normal haemoglobin levels) and ischaemic stroke has not been widely explored. The objective of this study is to establish a simple and economical marker for the detection of occult megaloblastosis at the community health care level in developing countries. A hundred patients who met the inclusion criteria were studied. At the 5% level of significance, the levels of cobalamin and folate were significantly lower, while the number of hypersegmented neutrophils on the peripheral smear was higher in patients from Group A (70 patients with high homocysteine) compared with the patients in Group B (30 patients with normal homocysteine). Forty-five (64.2%) of the 70 patients in Group A showed hypersegmentation of neutrophils in the peripheral smear. The high cost and difficulty in performing the vitamin assays limit their use as early markers of megaloblastosis. Hence, we conclude that in developing countries, the detection of hypersegmented neutrophils can be used at the primary healthcare level for early diagnosis of occult megaloblastosis, so that early therapeutic interventions with vitamins can prevent attacks of hyperhomocysteinemia-induced ischaemic stroke.

Topics: Anemia, Megaloblastic; Biomarkers; Brain Ischemia; Early Diagnosis; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Neutrophils; Primary Health Care; Stroke; Vitamin B 12

Although vitamin B12 deficiency is a well-known cause of hematological and neuropsychiatric illness, the presentation of combined severe pancytopenia, demyelination and prominent psychiatric impairment is rare.. We present a case of a previously healthy 55-year-old East African man with severe vitamin B12 deficiency (serum vitamin B12 22pmol/L) secondary to pernicious anemia. He had a severe hypoproliferative megaloblastic anemia with hemolysis (hemoglobin 61g/L, mean corpuscular volume 99fL, reticulocytes 0.8%, haptoglobin undetectable), leukopenia (2.7×109/L), thrombocytopenia (96×109/L), ataxia with central demyelination, and megaloblastic madness. The patient's anemia, myelopathy and psychiatric condition responded well to parenteral vitamin B12 replacement therapy, with significant improvement seen within weeks.. Hematological manifestations of vitamin B12 deficiency are typically inversely correlated with the presence and severity of neuropsychiatric impairment. Although uncommon, a presentation with severe hematological and neuropsychiatric disease can occur, as illustrated by this case. Its presence may help guide diagnosis as well as provide clinically important prognostic information.

Topics: Anemia, Megaloblastic; Diagnosis, Differential; Diagnostic Imaging; Humans; Leukopenia; Male; Mental Disorders; Middle Aged; Thrombocytopenia; Vitamin B 12; Vitamin B 12 Deficiency

The cblE disorder is an inherited disorder of vitamin B12 metabolism that results in elevated levels of homocysteine and decreased methionine in body fluids. Renal complications have been reported in patients with cblC disease, but not in those with cblE disease. The renal complications of cblC disease include thrombotic microangiopathy (TMA), neonatal hemolytic uremic syndrome, chronic renal failure, tubulointerstitial nephritis and proximal renal tubular acidosis. Previously, we reported a patient with cblC disease who had an atypical glomerulopathy that manifested with proteinuria and progressive renal insufficiency.. Studies were done on cultured fibroblasts. Renal biopsy tissue was examined by light and electron microscopy. There was decreased incorporation of labeled methyltetrahydrofolate and decreased synthesis of methylcobalamin. Complementation analysis placed the patient into the cblE complementation group. The findings from the histological and ultrastructural studies of renal biopsy were similar, but not identical, to those of idiopathic membranoproliferative glomerulonephritis (MPGN) and overlapped with those of TMA.. We describe a patient with cblE disease who had an atypical glomerulopathy similar to MPGN. Additional findings included migraine headaches, hypothyroidism and livedo reticularis.

Topics: Anemia, Megaloblastic; Biopsy; Cells, Cultured; Disease Progression; Female; Fibroblasts; Genetic Complementation Test; Genetic Predisposition to Disease; Glomerulonephritis, Membranoproliferative; Homocystinuria; Humans; Hydroxocobalamin; Hypothyroidism; Kidney; Livedo Reticularis; Migraine Disorders; Phenotype; Predictive Value of Tests; Renal Insufficiency, Chronic; Time Factors; Vitamin B 12; Vitamin B Complex; Young Adult

To analyze the causes of atrophic glossitis(AG) and to explore the relationship between AG and serum cobalamin, folate levels.. A total of 213 patients with AG treated from Jan.1979 to Jun. 2010 were analyzed for the causes of AG. Serum cobalamin, folate levels and complete blood count were tested in newly enrolled AG patients from Sep. 2010 to Aug. 2011. All data were analyzed with SPSS 16.0 software package for Student's t test.. There were 97 AG patients (45.4%) suffering from megaloblastic anemia (MA)/ macrocytosis. Among the 72 newly enrolled AG patients, fifty had cobalamin deficiency. Meanwhile, serum folate levels were increased in cobalamin deficiency group.. Cobalamin deficiency is the common cause both of MA/macrocytosis and AG, also may be the main cause of AG. Furthermore, AG may be the early clinical manifestation of cobalamin deficiency.

Topics: Anemia, Megaloblastic; Folic Acid; Glossitis; Humans; Vitamin B 12; Vitamin B 12 Deficiency

Cobalamin malabsorption accompanied by selective proteinuria is an autosomal recessive disorder known as Imerslund-Gräsbeck syndrome in humans and was previously described in dogs due to amnionless (AMN) mutations. The resultant vitamin B12 deficiency causes dyshematopoiesis, lethargy, failure to thrive, and life-threatening metabolic disruption in the juvenile period. We studied 3 kindreds of border collies with cobalamin malabsorption and mapped the disease locus in affected dogs to a 2.9Mb region of homozygosity on canine chromosome 2. The region included CUBN, the locus encoding cubilin, a peripheral membrane protein that in concert with AMN forms the functional intrinsic factor-cobalamin receptor expressed in ileum and a multi-ligand receptor in renal proximal tubules. Cobalamin malabsorption and proteinuria comprising CUBN ligands were demonstrated by radiolabeled cobalamin uptake studies and SDS-PAGE, respectively. CUBN mRNA and protein expression were reduced ~10 fold and ~20 fold, respectively, in both ileum and kidney of affected dogs. DNA sequencing demonstrated a single base deletion in exon 53 predicting a translational frameshift and early termination codon likely triggering nonsense mediated mRNA decay. The mutant allele segregated with the disease in the border collie kindred. The border collie disorder indicates that a CUBN mutation far C-terminal from the intrinsic factor-cobalamin binding site can abrogate receptor expression and cause Imerslund-Gräsbeck syndrome.

Topics: Anemia, Megaloblastic; Animals; Dogs; Exons; Female; Frameshift Mutation; Gene Expression Regulation; Humans; Ileum; Kidney; Malabsorption Syndromes; Male; Protein Binding; Proteinuria; Receptors, Cell Surface; RNA Stability; Vitamin B 12; Vitamin B 12 Deficiency

The cblG and cblC disorders of cobalamin (Cbl) metabolism are two inherited causes of megaloblastic anaemia. In cblG, mutations in methionine synthase (MTR) decrease conversion of hydroxocobalamin  (HOCbl) to methylcobalamin, while in cblC, mutations in MMACHC disrupt formation of cob(II)alamin (detected as HOCbl). Cases with undetectable methionine synthase (MS) activity are extremely rare and classified as 'cblG-variant'. In four 'cblG-variant' cases, we observed a decreased conversion of cyanocobalamin to HOCbl that is also seen in cblC cases. To explore this observation, we studied the gene defects, splicing products and expression of MS, as well as MS/MMACHC protein interactions in cblG-variant, cblG, cblC and control fibroblasts. We observed a full-size MS encoded by MTR-001 and a 124 kDa truncated MS encoded by MTR-201 in cblG, cblC, control fibroblasts and HEK cells, but only the MTR-201 transcript and inactive truncated MS in cblG-variant cells. Co-immunoprecipitation and proximity ligation assay showed interaction between truncated MS and MMACHC in cblG-variant cells. This interaction decreased 2.2, 1.5 and 5.0-fold in the proximity ligation assay of cblC cells with p.R161Q and p.R206W mutations, and HEK cells with knock down expression of MS by siRNA, respectively, when compared with control cells. In 3D modelling and docking analysis, both truncated and full-size MS provide a loop anchored to MMACHC, which makes contacts with R-161 and R-206 residues. Our data suggest that the interaction of MS with MMACHC may play a role in the regulation of the cellular processing of Cbls that is required for Cbl cofactor synthesis.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Anemia, Megaloblastic; Binding Sites; Carrier Proteins; Cells, Cultured; Gene Knockdown Techniques; HEK293 Cells; Humans; Hydroxocobalamin; Models, Molecular; Molecular Docking Simulation; Oxidoreductases; Protein Binding; Protein Isoforms; Protein Structure, Secondary; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Megaloblastic; Child, Preschool; Female; Foot; Hand; Humans; Hyperpigmentation; Malabsorption Syndromes; Proteinuria; Vitamin B 12; Vitamin B 12 Deficiency

Folate and vitamin B(12) metabolism are essential for de novo purine synthesis, and several defects in these pathways have been associated with immunodeficiency. Here we describe the occurrence of severe combined immunodeficiency (SCID) with megaloblastic anemia, leukopenia, atypical hemolytic uremic syndrome, and neurologic abnormalities in which hydroxocobalamin and folate therapy provided partial immune reconstitution. Whole exome sequencing identified compound heterozygous mutations in the MTHFD1 gene, which encodes a trifunctional protein essential for processing of single-carbon folate derivatives. We now report the immunologic details of this novel genetic cause of SCID and the response to targeted metabolic supplementation therapies. This finding expands the known metabolic causes of SCID and presents an important diagnostic consideration given the positive impact of therapy.

Topics: 3-Hydroxyacyl CoA Dehydrogenases; Anemia, Megaloblastic; Bone Marrow Examination; Cardiomyopathies; Combined Modality Therapy; DNA Mutational Analysis; Drug Combinations; Drug Therapy, Combination; Exome; Female; Genetic Carrier Screening; Humans; Hydroxocobalamin; Immunization, Passive; Infant; Infant, Newborn; Leukopenia; Lipid Metabolism, Inborn Errors; Methylenetetrahydrofolate Dehydrogenase (NADP); Minor Histocompatibility Antigens; Mitochondrial Myopathies; Mitochondrial Trifunctional Protein; Nervous System Diseases; Opportunistic Infections; Peripheral Nervous System Diseases; Pneumonia, Pneumocystis; Retinitis Pigmentosa; Rhabdomyolysis; Sequence Analysis, DNA; Severe Combined Immunodeficiency; Sulfadoxine; Trimethoprim; Vitamin B 12

Topics: Aged; Anemia, Megaloblastic; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Humans; Male; Pancytopenia; Treatment Outcome; Vitamin B 12; Vitamins

Topics: Adult; Anemia, Megaloblastic; Erythropoiesis; Female; Ferritins; Folic Acid; Hemoglobins; Humans; Iron; Iron Deficiencies; Vitamin B 12

The Imersland-Gräsbeck Syndrome (IGS) is a rare inherited disorder characterized by megaloblastic anemia due to a selective Vitamin B₁₂ malabsorption in association with mild proteinuria. This syndrome can be diagnosed and treated easily. Herein, we describe an infant with IGS as a rare etiology of growth retardation with diarrhea, vomiting and therapy-resistant proteinuria.

Topics: Anemia, Megaloblastic; Diarrhea, Infantile; Growth Disorders; Humans; Infant; Malabsorption Syndromes; Male; Proteinuria; Recurrence; Respiratory Tract Infections; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex; Vomiting

Inborn errors of cobalamin (Cbl, vitamin B(12)) absorption include hereditary intrinsic factor deficiency (HIFD) and Imerslund-Gräsbeck disease (IGD). HIFD is secondary to mutations in the HIF gene while IGD is due to mutations in one of the 2 subunits of the intrinsic factor receptor that is cubilin (CUBN) or amnionless (AMN). These disorders lead to intracellular Cbl depletion which in turn causes megaloblastic bone marrow failure, accumulation of homocysteine and methylmalonic acid (MMA), and methionine depletion. The clinical presentation reflects Cbl deficiency, with gastrointestinal symptoms, pancytopenia, and megaloblastic anemia. Mixed proteinuria, when it is present is strongly suggestive of IGD. Accurate diagnosis is always an emergency because early detection and treatment with life-long parenteral pharmacological doses of hydroxocobalamin are life saving and prevent further deterioration. However, the optimal frequency for cobalamin injections as a maintenance therapy is poorly reported. In order to evaluate the optimal maintenance schedule of cobalamin injections, we retrospectively collected clinical, biological, molecular and treatment data on 7 patients affected with congenital Cbl malabsorption. Unlike previous recommendations, we showed that a maintenance dosage of 1 mg cobalamin twice a year was enough to ensure a normal clinical status and keep the hematological and metabolic parameters in the normal range. These data suggest that patients affected with inborn errors of cobalamin absorption may be safely long-term treated with cobalamin injections every 6 months with careful follow-up of hematological and metabolic parameters. This maintenance regime is beneficial because the patients' quality of life improves.

Topics: Anemia, Megaloblastic; Child; Child, Preschool; Female; Genotype; Humans; Infant; Injections; Malabsorption Syndromes; Male; Membrane Proteins; Mutation; Proteins; Proteinuria; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency

Inherited malabsorption of cobalamin (Cbl) causes hematological and neurological abnormalities that can be fatal. Three genes have been implicated in Cbl malabsorption; yet, only about 10% of ~400-500 reported cases have been molecularly studied to date. Recessive mutations in CUBN or AMN cause Imerslund-Gräsbeck Syndrome (IGS), while recessive mutations in GIF cause Intrinsic Factor Deficiency (IFD). IGS and IFD differ in that IGS usually presents with proteinuria, which is not observed in IFD. The genetic heterogeneity and numerous differential diagnoses make clinical assessment difficult.. We present a large genetic screening study of 154 families or patients with suspected hereditary Cbl malabsorption. Patients and their families have been accrued over a period spanning >12  years. Systematic genetic testing of the three genes CUBN, AMN, and GIF was accomplished using a combination of single strand conformation polymorphism and DNA and RNA sequencing. In addition, six genes that were contenders for a role in inherited Cbl malabsorption were studied in a subset of these patients.. Our results revealed population-specific mutations, mutational hotspots, and functionally distinct regions in the three causal genes. We identified mutations in 126/154 unrelated cases (82%). Fifty-three of 126 cases (42%) were mutated in CUBN, 45/126 (36%) were mutated in AMN, and 28/126 (22%) had mutations in GIF. We found 26 undescribed mutations in CUBN, 19 in AMN, and 7 in GIF for a total of 52 novel defects described herein. We excluded six other candidate genes as culprits and concluded that additional genes might be involved.. Cbl malabsorption is found worldwide and genetically complex. However, our results indicate that population-specific founder mutations are quite common. Consequently, targeted genetic testing has become feasible if ethnic ancestry is considered. These results will facilitate clinical and molecular genetic testing of Cbl malabsorption. Early diagnosis improves the lifelong care required by these patients and prevents potential neurological long-term complications. This study provides the first comprehensive overview of the genetics that underlies the inherited Cbl malabsorption phenotype.

Topics: Anemia, Megaloblastic; Ethnicity; Female; Founder Effect; Genetic Association Studies; Genetic Heterogeneity; Genetic Testing; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Membrane Proteins; Mutation; Proteins; Proteinuria; Vitamin B 12; Vitamin B 12 Deficiency

Twenty cases of Dyphillobothrium pacificum (fish tapeworm) infections were prospectively studied to determine whether this tapeworm is associated with megaloblastic anemia, as commonly reported for D. latum infections. The most frequent symptoms were fatigue and mild abdominal pain, which were identified in approximately 66.6% of the 18 patients interviewed. Fourteen patients received treatment with niclosamide and all were cured. The other six patients spontaneously eliminated the tapeworms. One patient, who also had chronic diabetes and gastric atrophy, had low vitamin B12 levels and megaloblastic anemia. In all other patients, including three other patients with anemia, baseline vitamin B12 levels were in the reference range and did not significantly change when re-assessed three months later. Unlike D. latum, infection with D. pacificum is seldom associated with megaloblastic anemia or vitamin B12 deficit.

Topics: Adolescent; Adult; Aged; Anemia, Megaloblastic; Child; Child, Preschool; Diphyllobothriasis; Female; Humans; Male; Middle Aged; Vitamin B 12; Young Adult

We report the case of a 7-month-old breast fed infant who presented with a nose bleed and bruises. Investigation showed severe nutritional B12 deficiency anemia with a pancytopenia. It is important to take the nutritional history of both the infant and the mother for early prevention and treatment.

Topics: Anemia, Megaloblastic; Breast Feeding; Diet, Vegetarian; Humans; Infant; Male; Mothers; Pancytopenia; Severity of Illness Index; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency

Anemia is a common complication in malarial infection. Direct destruction and ineffective erythropoesis does not adequately explain the cause of anemia in malaria. We present a case with refractory megaloblastic anemia with asymptomatic falciparum malaria. We hypothesize that promoter variants in the inducible nitric oxide synthase gene might be the cause of severe refractory megaloblastic anemia and pancytopenia in our patient. Malaria should always be kept in mind as a cause of anemia especially in endemic areas even if the child is asymptomatic or there is no demonstrable parasite on routine smear examination.

Topics: Anemia, Megaloblastic; Antimalarials; Artemisinins; Artesunate; Child; Drug Therapy, Combination; Erythrocyte Transfusion; Fatal Outcome; Folic Acid; Humans; Malaria, Falciparum; Male; Nitric Oxide Synthase Type II; Pancytopenia; Plasmodium falciparum; Platelet Transfusion; Vitamin B 12; Vitamin B Complex

Current consensus supports the notion that proteinuria is a marker of renal disease with prognostic implications. Whereas most chronic kidney disease patients with proteinuria would often require antiproteinuric agents, there are some exceptions. Megaloblastic anemia type 1 (MGA1) is characterized by megaloblastic anemia due to congenital selective vitamin B(12) malabsorption and proteinuria. In the present study, we describe 2 Israeli Jewish patients with MGA1 and isolated proteinuria.. Because of their origin, the patients were screened for the presence of the already studied Tunisian AMN mutation, by direct sequencing the corresponding region from genomic DNA. PCR products were purified and sequenced.. Genomic DNA sequencing of the AMN gene of both patients confirmed that the acceptor splice site in intron 3 was changed from CAG to CGG (208-2A→G).. We determined the molecular basis of MGA1 in both patients and discuss the involvement of the cubilin/AMN complex in this pathology and its role in the development of the proteinuria. We also discuss the questionable significance of antiproteinuric treatment for these patients.

Topics: Anemia, Megaloblastic; Humans; Malabsorption Syndromes; Male; Membrane Proteins; Middle Aged; Mutation; Proteins; Proteinuria; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency

Derivatives of cobalamin (vitamin B(12)) are required for activity of two enzymes in humans. Adenosylcobalamin is required for activity of mitochondrial methylmalonylCoA mutase and methylcobalamin is required for activity of cytoplasmic methionine synthase. Deficiency in cobalamin, or inability to absorb cobalamin normally, can result in accumulation of methylmalonic acid and homocysteine in blood and urine. Methylmalonic acidemia can result in metabolic acidosis which in severe cases may be fatal. Hyperhomocysteinemia along with hypomethioninemia can result in hematologic (megaloblastic anemia, neutropenia, thrombocytopenia) and neurologic (subacute combined degeneration of the cord, dementia, psychosis) defects. Inborn errors affecting cobalamin absorption (inherited intrinsic factor deficiency, Imerslund–Gra¨ sbeck syndrome) and transport (transcobalamin deficiency) have been described. A series of inborn errors of intracellular cobalamin metabolism, designated cblA-cblG, have been differentiated by complementation analysis. These can give rise to isolated methylmalonic acidemia (cblA, cblB, cblD variant 2), isolated hyperhomocysteinemia (cblD variant 1, cblE, cblG) or combined methylmalonic acidemia and hyperhomocysteinemia (cblC, classic cblD, cblF). All these disorders are inherited as autosomal recessive traits. The genes underlying each of these disorders have been identified. Two other disorders, haptocorrin deficiency and transcobalamin receptor deficiency, have been described, but it is not clear that they have any consistent clinical phenotype.

Topics: Amino Acid Metabolism, Inborn Errors; Anemia, Megaloblastic; Cobamides; Homocysteine; Humans; Hyperhomocysteinemia; Infant, Newborn; Malabsorption Syndromes; Metabolism, Inborn Errors; Methylmalonic Acid; Methylmalonyl-CoA Mutase; Neonatal Screening; Proteinuria; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia; Anemia, Megaloblastic; Biomarkers, Tumor; Diagnosis, Differential; Erythroblasts; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Neutropenia; Severity of Illness Index; Vitamin B 12; Vitamin B 12 Deficiency

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adolescent; Amoxicillin; Anemia, Megaloblastic; Anti-Bacterial Agents; Clarithromycin; Helicobacter Infections; Helicobacter pylori; Humans; Lansoprazole; Male; Pancytopenia; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Megaloblastic; Anemia, Pernicious; Autoantibodies; Autoimmune Diseases; Folic Acid Deficiency; Gastritis, Atrophic; Humans; Intrinsic Factor; Parietal Cells, Gastric; Vitamin B 12; Vitamin B 12 Deficiency

Vitamin B12 deficiency is an uncommon cause of pyrexia. We report the case of a patient who presented with pyrexia and anaemia, which after exclusion of infective, inflammatory or endocrine causes was attributed to megaloblastic anaemia secondary to vitamin B12 deficiency. The patient's fever responded to treatment of vitamin B12 deficiency.

Topics: Adolescent; Anemia, Megaloblastic; Diagnosis, Differential; Fever; Humans; Male; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency

Vitamin B12 deficiency in infants often presents with nonspecific hematological, gastrointestinal, and neurological manifestations. It is usually caused by inadequate intake, abnormal absorption, or congenital disorders of vitamin B12 metabolism, including transport disorders. We describe a vitamin B12-deficient infant with severe anemia who was breastfed. His mother had undiagnosed vitamin B12 deficiency having undergone total gastrectomy 18 years earlier. The infant developed normally after taking vitamin B12. It is important to suspect vitamin B12 deficiency in mothers who have undergone gastrectomy. Early diagnosis and treatment of vitamin B12 deficiency in infants is important and will help improve long-term prognosis.

Topics: Anemia, Megaloblastic; Atrophy; Brain; Humans; Infant; Male; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency

Leukocytosis, splenomegaly, and an increased vitamin B(12) level are characteristic findings of chronic myelogenous leukemia in the chronic phase (CML-CP). Here, we report a patient with CML-CP accompanied by megaloblastic anemia. A 61-year-old man consulted our hospital because of anemia and thrombocytopenia. On physical examination, there were no remarkable findings; there was no hepatosplenomegaly. Laboratory findings were: hemoglobin 6.0 g/dl; MCV 113.6 fl; platelet count 100×10(9)/l; white cell count 8.66×10(9)/l; and LDH 1,236 IU/l. Peripheral blood smear demonstrated hypersegmented neutrophils and megalocytes with emergence of myeloblasts, giant metamyelocytes, and nucleated red cells. Vitamin B(12) and folic acid levels were low. Bone marrow examination showed megaloblastic change in the erythroblasts and myeloid hyperplasia. Following vitamin B(12) and folic acid administration, anemia and thrombocytopenia rapidly improved; thereafter, marked leukocytosis became evident. Based on the presence of t(9;22)(q34;q11) on cytogenetic study and a positive result for Major bcr/abl fusion gene, a diagnosis of CML-CP was established. This case illustrates that ineffective erythropoiesis results in anemia and thrombocytopenia in CML with vitamin B12 and/or folic acid deficiency.

Topics: Anemia, Megaloblastic; Diagnosis, Differential; Erythropoiesis; Folic Acid; Folic Acid Deficiency; Fusion Proteins, bcr-abl; Humans; Karyotyping; Leukemia, Myeloid, Chronic-Phase; Male; Middle Aged; Thrombocytopenia; Translocation, Genetic; Vitamin B 12; Vitamin B 12 Deficiency

Measurement of serum cobalamin levels is the standard investigation for assessing Vitamin B12 deficiency. However some patients with clinical evidence of cobalamin deficiency may have serum levels within the normal range. Since falsely increased values of cobalamin can be caused by alcoholic liver disease, we evaluated the impact of this disease on the diagnosis of cobalamin and folic acid deficiency.. We reviewed data of 101 adult patients with megaloblastic anemia assessed by measuring in parallel serum cobalamin, serum folate and red blood cell folate levels. Further tests were performed in order to find the cause of megaloblastosis. All patients were treated with cobalamin and/or folic acid therapy.. Vitamin B12, folate and both deficiency were found in 86, 5 and 6 cases respectively. Normal cobalamin serum levels, normal serum and erythrocyte folate levels were found only in 3 patients, all alcohol-dependent, while in another alcoholic borderline vitamin B12 serum levels were found. All the four patients responded to cobalamin treatment.. Some alcohol-dependent patients with megaloblastic anemia may respond to vitamin B12 treatment despite normal cobalamin serum levels; therefore in alcoholics caution is urged in the interpretation of these vitamin assays, because of possible functional vitamin B12 deficiency.

Topics: Adult; Aged; Aged, 80 and over; Alcoholism; Anemia, Megaloblastic; Erythrocytes; Female; Folic Acid; Hemoglobins; Humans; Male; Middle Aged; Retrospective Studies; Vitamin B 12; Vitamin B 12 Deficiency; Young Adult

In developing countries, nutritional vitamin B(12) deficiency in infants due to maternal diet without adequate protein of animal origin has some characteristic clinical features. In this study, haematological, neurological and gastrointestinal characteristics of nutritional vitamin B(12) deficiency are presented.. Hospital records of 27 infants diagnosed in a paediatric haematology unit between 2000 and 2008 were evaluated retrospectively.. The median age at diagnosis was 10.5 months (3-24 months). All the infants were exclusively breast fed and they presented with severe nonspecific manifestations, such as weakness, failure to thrive, refusal to wean, vomiting, developmental delay, irritability and tremor in addition to megaloblastic anaemia. The diagnosis was confirmed by complete blood counts, blood and marrow smears and serum vitamin B(12) and folic acid levels. The median haemoglobin level was 6.4 g/dL (3.1-10.6) and mean corpuscular volume (MCV) was 96.8 fL (73-112.3). Some patients also had thrombocytopaenia and neutropaenia. All the infants showed clinical and haematological improvement with vitamin B(12) administration. Patients with severe anaemia causing heart failure received packed red blood cell transfusions as the initial therapy.. Paediatricians must consider nutritional vitamin B(12) deficiency due to maternal dietary deficiency in the differential diagnosis of some gastrointestinal, haematological, developmental and neurological disorders of infants with poor socioeconomic status. Delay in diagnosis may cause irreversible neurological damage.

Topics: Anemia, Megaloblastic; Child, Preschool; Female; Humans; Infant; Infant Food; Infant, Newborn; Male; Maternal Welfare; Nutritional Status; Retrospective Studies; Risk Factors; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Aged; Anemia; Anemia, Megaloblastic; Cytokinesis; Fibroblasts; Humans; Male; Vitamin B 12

A 14 year male adolescent born of 2nd degree consanguineous marriage presented with asymptomatic proteinuria and severe anemia. He had leucopenia, anisopoikilocytosis, megaloblastic erythropoiesis, megakaryocytes with low serum B12 level. His younger sibling was similarly affected. This combination suggested Imerslund-Grasbeck syndrome. The hemoglobin levels improved with injection of vitamin B12 but proteinuria persisted. During follow-up, he developed ketoacidosis due to insulin dependent diabetes mellitus. This rare combination has not been reported in the Indian literature.

Topics: Adolescent; Anemia, Megaloblastic; Child; Diabetes Mellitus, Type 1; Failure to Thrive; Humans; Hyperpigmentation; Intestinal Absorption; Malabsorption Syndromes; Male; Mutation, Missense; Prevalence; Risk Factors; Syndrome; Vitamin B 12; Vitamin B 12 Deficiency

Megaloblastic anemias are basically caused by vitamin B(12) and/or folic acid deficiency. Childhood vitamin B(12) deficiency is extremely rare. There are congenital and acquired forms of vitamin B(12)-deficiency anemias. The article captures findings of 10 year observation of 3 patients with Imerslund-Gräsbeck Syndrome (congenital chronic megaloblastic anemia with proteinuria), in which the diagnosis was established by us in early childhood and due to correct treatment and prevention complete clinical-laboratory remission is kept so far. We have also observed rare case of acquired megaloblastic anemia - 14 years old vegetarian patient, who was diagnosed with vitamin B(12)-deficiency anemia based on history, clinical and para-clinical data. It was caused by strict vegetarianism of the patient. Therefore first of all the diet was corrected. In 5 days of specific treatment with vitamin B(12) "reticulocyte crisis" was manifested (proving the correctness of diagnosis and treatment) and complete clinical-hematological remission was achieved in 2 weeks. The given cases are interesting as megaloblastic anemias in childhood are both rare and difficult to diagnose. In such cases timely diagnosis, treatment and prevention tactics should be based on cause-and-effect relation of disease.

Topics: Adolescent; Anemia, Megaloblastic; Female; Humans; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex

To investigate the status of vitamin B12 deficiency in elderly inpatients in the department of neurology.. A total number of 827 patients in the department of neurology of Shanghai Punan hospital, from March 2007 to July 2008, were employed in the present study. They were 60 years or older, and the average age was 77.1+/-7.5 years old. All the patients were diagnosed with no severe hepatic or renal dysfunction, without any usage of vitamin B12 during the previous 3 months before the detection. The levels of serum vitamin B12, folate and homocysteine (Hcy) were evaluated. The patients with vitamin B12 deficiency were screened. The resulting symptoms, positive signs of neurological examination, and the neuroelectricphysiological results were compared between patients with or without vitamin B12 deficiency.. Vitamin B12 deficiency was found in 163 patients (19.71% of the total patients), and was more prevalent in female than in male patients, also with increased incidences with aging. Patients with low levels of serum vitamin B12 exhibited higher rate of gastrointestinal diseases, while only 9.82% of the vitamin B12 deficient patients had megaloblastic anemia. Symptoms of vitamin B12 deficiency included unsteadily walking in the darkness and hypopallesthesia, and some chronic diseases such as cerebral ischemia, hypertension, Parkinson's disease (Parkinsonism), diabetes mellitus and coronary heart disease. Most of the vitamin B12 deficient patients had neuroelectricphysiological abnormalities.. Vitamin B12 deficiency is remarkably common in elderly patients in neurology department, with various and atypical clinical manifestations, and the neurological symptoms are more common than megaloblastic anemia symptoms.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Anemia, Megaloblastic; Electrophysiology; Female; Folic Acid; Geriatric Assessment; Homocysteine; Humans; Male; Middle Aged; Neurologic Examination; Neuropsychological Tests; Nutritional Status; Prevalence; Retrospective Studies; Risk Factors; Sex Factors; Statistics as Topic; Vitamin B 12; Vitamin B 12 Deficiency

Megaloblastic anemias are a subgroup of macrocytic anemias, in which distinctive morphologic abnormalities occur in red cell precursors in bone marrow, namely megaloblastic erythropoiesis. Of the many causes of megaloblastic anemia, the most common are disorders resulting from cobalamin or folate deficiency. The clinical symptoms are weakness, fatigue, shortness of breath and neurologic abnormalities. The presence of oral signs and symptoms, including glossitis, angular cheilitis, recurrent oral ulcer, oral candidiasis, diffuse erythematous mucositis and pale oral mucosa offer the dentist an opportunity to participate in the diagnosis of this condition. Early diagnosis is important to prevent neurologic signs, which could be irreversible. The aim of this paper is to describe the oral changes in a patient with megaloblastic anemia caused by a dietary deficiency of cobalamin.

Topics: Adult; Anemia, Megaloblastic; Female; Humans; Hydroxocobalamin; Mouth Diseases; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex

Pregnant women with low B12 levels are unable to provide the necessary amount of this vitamin to their fetuses. The mothers are usually not anemic, and failure to thrive and neurologic deficits are more common in their infants than in megaloblastic anemia. We report the case of a newborn that was born to a vegetarian mother and presented with the symptoms of megaloblastic anemia at birth; we also discuss vitamin B12 metabolism during pregnancy and lactation. An interesting feature of the present case is that it is the only reported case of a newborn that was treated by supplementation of the mother.

Topics: Adult; Anemia, Megaloblastic; Breast Feeding; Female; Humans; Infant, Newborn; Lactation; Mothers; Pregnancy; Treatment Outcome; Vitamin B 12

Nutritional B12 deficiency in childhood is an uncommon disorder. Most cases are due to maternal insufficiency, resulting from deficient stores and intake, and is generally seen in exclusively breast fed infants. This report describes a breast-fed infant with megaloblastic anemia secondary to maternal vitamin B12 deficiency. We describe this patient to remind readers that B12 deficiency may cause severe pancytopenia and regression of motor functions. These patients can present with unexpected signs and symptoms, such as developmental delay and regression as in our patient. It is also important to take the nutritional history of both the child and the mother of early prevention and treatment. With early awareness and appropriate measures potentially irreversible neurologic damage can be prevented in the infant.

Topics: Anemia, Megaloblastic; Breast Feeding; Humans; Infant; Male; Pancytopenia; Vitamin B 12; Vitamin B 12 Deficiency

Epileptic seizures during infancy have a wide variety of clinical presentations and the outcome differs according to the etiology. Among the benign and rare causes of infantile seizures, Vitamin B12 deficiency has been encountered. Common symptoms of Vitamin B12 deficiency in infants include megaloblastic anemia, feeding difficulties, developmental delay, microcephaly, failure to thrive, hypotonia, lethargy, irritability, involuntary movements, seizures and cerebral atrophy. Involuntary movements and seizures may rarely be the initial symptoms of Vitamin B12 deficiency. Involuntary movements have also been reported to appear after initiation of Vitamin B12 supplementation in isolated cases, whereas, no such information exits for seizures. In this paper, three infants with Vitamin B12 deficiency associated with motor and mental retardation are reported because of long-lasting focal/multifocal epileptic seizures following the initiation of intramuscular Vitamin B12 treatment. Antiepileptics were introduced in addition to Vitamin B12. Seizures disappeared within a few days or weeks; electroencephalographic findings were normalized in a few months. No relapses occurred during the follow-up period.

Topics: Anemia, Megaloblastic; Anticonvulsants; Electroencephalography; Female; Humans; Infant; Male; Seizures; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex

We report the case of a 7 month-old girl that presented with acute anemia, generalized muscular hypotonia and failure to thrive. Laboratory evaluation revealed cobalamin deficiency, due to a vegan diet of the mother. The clinical triad of an acquired floppy baby syndrome with megaloblastic anemia and failure to thrive is pathognomic for infantile cobalamin deficiency. Neurological abnormalities are often irreversible and may be associated with delayed myelinization in the MRI. A normal cobalamin level in maternal serum and absence of anemia do not exclude subclinical deficiency. If cobalamin deficiency is suspected, e.g. in pregnant women on vegan diet, urinary methylmalonic acid excretion and plasma homocysteine levels should be determined and cobalamin substitution should be started at an early stage to avoid potentially irreversible damage of the fetus.

Topics: Anemia, Megaloblastic; Bone Marrow Examination; Diagnosis, Differential; Diet, Vegetarian; Failure to Thrive; Female; Follow-Up Studies; Humans; Hydroxocobalamin; Infant; Injections, Intravenous; Pregnancy; Pregnancy Complications; Time Factors; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency

In developing countries, a deficiency of cobalamine and folate contributes significantly to megaloblastic anaemia. Neurological observations in infants and young children with megaloblastic anaemia have included hypotonia, developmental regression, tremors and other abnormal movements. Following therapy with vitamin B12, coarse tremors occurred in six of 51 patients (12%) with megaloblastic anaemia. The tremors, which were noticed initially in the hands and feet, gradually became generalised and disappeared during sleep. They subsided within 5-11 days. Thirteen of 25 (52%) patients developed thrombocytosis between day 3 and week 5 of follow-up. In one child, the platelet count increased to >1300 x 10(9)/L. The importance of recognising these clinical findings during treatment of megaloblastic anaemia is emphasised.

Topics: Anemia, Megaloblastic; Child; Child, Preschool; Developing Countries; Folic Acid; Folic Acid Deficiency; Humans; India; Infant; Platelet Count; Thrombocytosis; Tremor; Vitamin B 12; Vitamin B 12 Deficiency

We aimed to investigate the presence of psychomotor retardation, physical and laboratory examination in infants with megaloblastic anemia. Inclusion criteria for the study were; age 9 to 36 months, refusal of food except for breast and cow milk, loss of appetite, developmental delay, significant pallor, and hypersegmentation neutrophils in the peripheral blood smear. A total of 33 children fulfilling the inclusion criteria were enrolled among 3368 patients attending Pediatric Outpatient Clinics of şirnak-Cizre State Hospital between January 25, 2004 and May 5, 2004. Mean age was 16.4 months. Thirty-two patients had Vitamin B12 deficiency, 1 patient had folate deficiency, and 10 patients had combined vitamin B12 and folate deficiency. Statistically, a positive significant relationship was detected between serum vitamin B12 levels and mean corpuscular volume (P = 0.001, r = 0.56), and between vitamin B12 levels and hemoglobin (P = 0.004, r = 0.49). We believe that preventative measures such as fortification of flour with vitamin B12, nutritional support with vitamin B12 for the mother during pregnancy and nursing, provision of adequate primary preventive health services, and starting complementary food after 6 months of age are important determinants for preventing megaloblastic anemia.

Topics: Anemia, Megaloblastic; Child, Preschool; Female; Folic Acid; Folic Acid Deficiency; Humans; Infant; Intellectual Disability; Male; Motor Skills Disorders; Neutrophils; Turkey; Vitamin B 12; Vitamin B 12 Deficiency

Vitamin B(12) deficiency is a well-known cause of recurrent aphthous stomatitis (RAS). However, the mechanism by which this deficiency causes the stomatitis is not well understood. Imerslund-Grasbeck syndrome (IGS) causes vitamin B(12) deficiency and proteinuria due to a defect in the vitamin B(12) receptor. We sought to determine whether the RAS observed in IGS patients is associated with neutrophil dysfunction. We report 3 infants with vitamin B(12) deficiency due to IGS, who presented with borderline or normal hemoglobin concentrations, RAS, and a neutrophil function defect. All 3 patients were homozygous for a splice site mutation affecting exon 4 of the AMN gene. A direct correlation was observed between low serum vitamin B12 levels and defective neutrophil function (low chemotaxis and elevated superoxide production) in the patients. Vitamin B(12) therapy led to an immediate resolution of aphthous stomatitis and full correction of neutrophil function. We demonstrated that serum vitamin B(12) deficiency is associated with a neutrophil chemotactic defect and RAS in IGS patients. We suggest that the RAS observed in these patients is due to this defect.

Topics: Anemia, Megaloblastic; Chemotaxis; Consanguinity; Diseases in Twins; Female; Humans; Infant; Leukocyte Disorders; Male; Membrane Proteins; Mutation; Neutrophils; Proteins; Stomatitis, Aphthous; Superoxides; Syndrome; Vitamin B 12; Vitamin B Deficiency

Fifty (50) cases of Leishmaniasis were included in a prospective study after making the diagnosis based on the demonstration of L D Bodies on bone marrow aspirate. Hemoglobin (Hb) and total leucocyte count (TLC) were less than 10 gm/dl and 4000 per/ml respectively in 22 out of 50 cases. Among 50 cases, 30 showed macrocytic red cell and hypersegmented neutrophils on peripheral blood smear as features of megaloblastic anemia. Out of 30 cases of leishmaniasis with megaloblastic anemia, 10 cases showed decreased reticulocyte count. Bone marrow aspiration cytology showed megaloblastic maturation in erythroid series and giant metamyelocytes in myeloid series in all 30 cases of leishmaniasis with megaloblastic changes. Bone marrow iron was also increased in these cases. However megakaryocyte was normal in all. Among 30 cases of leishmaniasis with megaloblastic changes, 15 cases were treated with sodium antimony gluconate (SAG) only and other 15 with SAG, folic acid and Vit. B12. Rest 20 cases of leishmaniasis without megaloblastic changes were also treated with SAG only. After treatment with SAG alone as well as with SAG, folic acid and vit. B12, hemoglobin and TLC improved in all 50 cases. Of 15 cases of leishmaniasis with megaloblastic changes, who were treated with SAG, folic acid and vit. B12, the reticulocyte count reached at peak on the 7th day and normalized at the end of 4th week. Red blood cells (RBC) also became normocytic normochromic and neutrophils became normal on peripheral blood smear. But no change was observed in reticulocyte count, RBC and white blood cell (WBC) morphology on peripheral blood smear in cases of leishmaniasis without megaloblastic changes and other 15 cases of leishmaniasis with megaloblastic changes, who received SAG only.

Topics: Anemia, Megaloblastic; Antimony Sodium Gluconate; Drug Therapy, Combination; Female; Folic Acid; Hospitals; Humans; Incidence; Leishmaniasis, Visceral; Male; Nepal; Prospective Studies; Reticulocyte Count; Treatment Outcome; Vitamin B 12

Topics: Administration, Oral; Anemia, Megaloblastic; Anemia, Pernicious; Antibodies; Folic Acid; Folic Acid Deficiency; Humans; Injections, Intramuscular; Intrinsic Factor; Leucovorin; Schilling Test; Vitamin B 12; Vitamin B Complex

Topics: Administration, Oral; Anemia, Megaloblastic; Follow-Up Studies; Humans; Injections, Intramuscular; Patient Compliance; Randomized Controlled Trials as Topic; Time Factors; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex

We report a case of anaphylactic reaction to intramuscular injection of cyanocobalamin. This 52-year-old lady was diagnosed as a case of megaloblastic anemia secondary to dietary vitamin B12 deficiency. She had severe anaphylactic reaction after the parenteral administration of cyanocobalamine. Later she received oral vitamin B12 with no adverse effects. The purpose of this case report is to draw attention to the hypersensitive reaction to injectable vitamin B12, which is rarely seen. This could be due to sensitization to the vitamin B12 molecule itself or an IgE mediated reaction. We concluded that anaphylactic reaction to vitamin B12 is a rare but serious side effect and it should be kept in mind while the drug is being administered to the patient, especially via the parenteral route.

Topics: Anaphylaxis; Anemia, Megaloblastic; Female; Humans; Injections, Intramuscular; Middle Aged; Vitamin B 12; Vitamin B 12 Deficiency

There is increased worldwide concern about the consequences of folic acid and vitamin B12 deficiencies on health, which include megaloblastic anemia, neural tube defects and cardiovascular disease.. This study intended to determine the prevalence of folic acid and vitamin B12 deficiencies in vulnerable groups in labor and poor socioeconomic strata of the Venezuelan population.. A total of 5658 serum samples were processed to determine folic acid and vitamin B12 concentrations. The study involved three surveys performed during 2001-2002 and included infants, children, adolescents and pregnant women from labor and poor socioeconomic strata of the population. The method used was a radio immunoassay designed for the simultaneous measurement of serum folic acid and vitamin B12.. The prevalence of folic acid deficiency was higher than 30% for all groups studied, reaching 81.79% in adolescents. Vitamin B12 deficiency was 11.4% in samples collected nationwide, but there was also a similar prevalence of high serum levels. The prevalence of folic acid and vitamin B12 deficiencies in pregnant women reached 36.32 and 61.34%, respectively.. This work shows that there is a high prevalence of folic acid deficiency, especially in women of reproductive age, pregnant adolescents and in the whole population studied in Vargas state. This situation requires immediate intervention as supplementation or food fortification programs.

Topics: Adolescent; Adult; Anemia, Megaloblastic; Cardiovascular Diseases; Child; Child, Preschool; Female; Folic Acid; Folic Acid Deficiency; Humans; Infant; Male; Neural Tube Defects; Nutrition Surveys; Pregnancy; Radioimmunoassay; Seroepidemiologic Studies; Venezuela; Vitamin B 12; Vitamin B 12 Deficiency

A 4-base deletion has been identified in the coding region of the gene for gastric intrinsic factor (IF) in an 11-year-old girl with severe anemia and cobalamin (Cbl) deficiency. The bone marrow showed frank megaloblastic morphology, and the Schilling test indicated a failure to absorb Cbl that was corrected by coadministration of IF. Pentagastrin administration induced acid secretion, but the gastric juice lacked IF as determined by CbI binding, by fractionation of protein-bound CbI, and by immunoprecipitation with anti-IF antiserum. Individual exons were amplified by the polymerase chain reaction by using primers to the flanking intronic regions, and the nucleotide sequence analysis identified a 4-base deletion (c183_186delGAAT) spanning positions 104 to 107 in exon 2, resulting in premature termination of translation. This mutation also eliminates a site for Bst XI endonuclease and introduces a site for BsaBI for identifying this deletion in hereditary IF deficiency.

Topics: Anemia, Megaloblastic; Child; Female; Gastric Juice; Gene Deletion; Humans; Intrinsic Factor; Pentagastrin; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adult; Anemia, Megaloblastic; Female; Fetal Blood; Folic Acid; Homocysteine; Humans; Infant, Newborn; Maternal-Fetal Exchange; Pregnancy; Vitamin B 12

A 61-year-old eutrophic male was diagnosed with vitamin B12 deficiency and megaloblastic anemia. A modified Schilling test suggested intestinal malabsorption unrelated to intrinsic factor deficiency. Subsequent colonoscopy revealed the presence of a Taenia tapeworm. The anemia resolved within days under therapy with niclosamide and temporary vitamin B12 supplements. The present case suggests that, in addition to other well-known parasitic agents, e.g., Diphyllobothrium latum and Giardia lamblia, Taenia infestation can also be a cause of intestinal vitamin B12 malabsorption.

Topics: Anemia, Megaloblastic; Animals; Anthelmintics; Food Parasitology; Humans; Intestinal Diseases, Parasitic; Malabsorption Syndromes; Male; Meat; Middle Aged; Niclosamide; Taeniasis; Vitamin B 12; Vitamin B 12 Deficiency

The abnormalities in iron metabolism associated with megaloblastic anemia are rapidly reversed by B(12) therapy in pernicious anemia (PA). Although non-tranferrin-bound plasma iron (NTBI) was previously shown to be associated with severe iron overload, its origin is unknown.. Four patients with PA were studied before and after B(12) treatment. NTBI was measured by a fluorescence-based one-step assay. All patients had very high transferrin saturation, NTBI values ranging from 1.1 to 2.6 micromol/l and normal serum ferritins. B(12) treatment resulted in the disappearance of NTBI and normalization of transferrin saturation within 22-42 h.. The prompt disappearance of NTBI following B(12) therapy implicates catabolic iron derived from ineffective erythropoiesis as the major source of NTBI in untreated PA and possibly in thalassemia major and sideroblastic anemia. Our findings offer further insight into the pathogenesis of NTBI in diseases associated with abnormal erythropoiesis.

Topics: Adult; Aged; Anemia, Megaloblastic; Erythropoiesis; Female; Ferritins; Humans; Iron; Iron Overload; Male; Middle Aged; Transferrin; Vitamin B 12

The results of examinations of reticulocytes in blood samples of 12 patients with the confirmed diagnosis of B12-deficit anemia and of 20 virtually healthy subjects (control group) by means of the GEN-S hematological analyzer (Beckman-Coulter) are described in the paper. Typical changes of the reticulocyte parameters are defined and their dynamics (with treatment by Vitamin B12) is studied. It was established that the additional parameters of the reticulocyte analysis, characterizing the quantity of immature reticulocytes and the fraction of immature reticulocytes, increase by 3 days before the total quantity of erythrocytes increases, which means that the above parameters can be used earlier as criteria in evaluating the treatment efficiency.

Topics: Adult; Anemia, Megaloblastic; Autoanalysis; Female; Humans; Male; Middle Aged; Reference Values; Reticulocyte Count; Reticulocytes; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Administration, Oral; Anemia, Megaloblastic; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Injections, Intramuscular; Prospective Studies; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency

We present 62 yrs old patient in whom megaloblastic anaemia due to vitamin B12 depletion was caused by Helicobacter pylori infection. An eradication treatment with the vitamin B12 supplementation within 7 days resulted in withdrawal of the abnormalities in the blood smear. The inflammation of gastric mucosa with intestine metaplasia is still observed. According to the letters these changes may persist up to 2-3 years after treatment ending.

Topics: Anemia, Megaloblastic; Gastric Mucosa; Helicobacter Infections; Humans; Male; Middle Aged; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency

The authors describe a 16-month-old infant presenting with neurologic developmental regression, severe pancytopenia, excessive skin pigmentation, and tremor resulting from nutritional vitamin B12 deficiency. She had been exclusively breast-fed and had refused to take any other food. Laboratory studies showed severe pancytopenia, a decrease in serum B12 levels, and an increase in urinary methylmalonic acid levels. Bone marrow aspiration was compatible with megaloblastic changes. Schilling test was normal. The serum B12 level of the mother was also low. Megaloblastic anemia resulting from inadequate B12 intake was diagnosed. Parenteral B12 therapy was initiated. The neurologic picture did not completely resolve, but pancytopenia, tremor, and hyperpigmentation of the extremities recovered completely.

Topics: Anemia, Megaloblastic; Female; Humans; Hyperpigmentation; Infant; Pancytopenia; Treatment Outcome; Tremor; Vitamin B 12; Vitamin B 12 Deficiency

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Anemia, Megaloblastic; Anemia, Pernicious; Animals; Bone Marrow Cells; Deoxyuracil Nucleotides; DNA; Folic Acid; Folic Acid Deficiency; Humans; Rats; Vitamin B 12; Vitamin B 12 Deficiency

In rats, in contrast with human subjects who develop megaloblastic anaemia due to vitamin B12 deficiency, haematological abnormalities with anaemia were not observed under normoxic conditions even though plasma vitamin B12 concentration was reduced to <15 % of a normal concentration by depleting dietary vitamin B12. To elucidate whether erythropoiesis was affected by vitamin B12 deficiency in rats, these vitamin B12-deficient rats were exposed to hypoxia (10.5 % O2) to stimulate erythropoiesis. In the vitamin B12-sufficient control rats, erythrocyte count was significantly (P<0.05) increased 1 week after starting the hypoxic exposure. However, the hypoxia-induced erythropoiesis was affected by vitamin B12 deficiency, and no significant increase in the erythrocyte count was observed even after 6-week exposure to hypoxia in the vitamin B12-deficient rats. In the vitamin B12-deficient rats in hypoxia, erythrocytes became abnormally enlarged, and haemoglobin concentration in peripheral blood was increased in proportion to the increase of mean corpuscular volume. However, the level of the increase in the haemoglobin concentration was significantly (P<0.05) lower in the vitamin B12-deficient rats compared with that in the -sufficient controls. In addition, in the vitamin B12-deficient rats, in contrast to the -sufficient rats, serum erythropoietin concentration was not normalized even after 6-week exposure to hypoxia. These results indicate that a megaloblastic anaemia-like symptom is induced when the vitamin B12-deficient rats are exposed to hypoxia.

Topics: Analysis of Variance; Anemia, Megaloblastic; Animals; Erythrocyte Count; Erythropoietin; Hypoxia; Male; Methylmalonic Acid; Models, Animal; Rats; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Megaloblastic; Humans; Nitrous Oxide; Vitamin B 12

Transcobalamin (TC), a vitamin B12 (cobalamin, Cbl) binding protein in plasma, promotes the cellular uptake of the vitamin by receptor-mediated endocytosis. Inherited TC deficiency is an autosomal recessive disorder characterized by megaloblastic anaemia caused by cellular vitamin B12 depletion. It may be accompanied by neurological complications, including a delay in psychomotor and mental development. This report describes three sisters with inherited TC deficiency resulting from a splicing defect in the TC gene. A point mutation was identified in intron 3 splice site of the TC gene that activates a cryptic splice site in exon 3. The transcript generated has an in-frame deletion of 81 nucleotides and the resulting truncated protein is unstable and not secreted by the cells. Until now, genetic studies have been reported in only five patients with TC deficiency and the molecular defect was different in each of them, which gives evidence for a genetic heterogeneity of the disease.

Topics: Adult; Anemia, Megaloblastic; Animals; Child; COS Cells; Electrophoresis, Polyacrylamide Gel; Female; Genotype; Humans; Male; Parents; Point Mutation; Reverse Transcriptase Polymerase Chain Reaction; RNA Splice Sites; Siblings; Transcobalamins; Transfection; Vitamin B 12

A 40-year-old woman was admitted to our hospital because of pancytopenia with megaloblastic anemia. Two months later she complained of rapidly progressive gait disturbance and numbness in the distal part of limbs. She also told that her hair had turned totally gray in the third decade. Neurologically, mental state, cranial nerves and cerebellar functions were normal. Superficial sensations were impaired below the lower thoracic level and deep sensations were completely lost in the lower limbs. Moderate weakness was found in the lower limbs, symmetrically. Deep tendon reflexes were diminished in the upper limbs and absent in the lower limbs. Babinski's reflex was positive bilaterally. MR images of the spinal cord showed hyperintensity in the posterior column below the thoracic cord. Although the serum level of vitamin B12 was within normal range, serum homocysteine level was elevated markedly. Under the diagnosis of subacute combined degeneration (SCD) due to possible vitamin B12 deficiency, the treatment with intravenous injections of 500 micrograms/day of mecobalamin was undertaken. Muscle strength and sensory impairment improved progressively and she became able to walk with a cane. The coloration of her gray hair was also noted. After treatment, pancytopenia and megaloblastic anemia also markedly improved. Vitamin B12 became high in serum concentration and the serum level of homocysteine became normal. These clinical and laboratory findings support the diagnosis of SCD with normal serum level of vitamin B12 in our case, suggesting that the level of vitamin B12 in serum does not always correlate with that in tissue and, therefore, SCD should not be excluded just only by the reason of normal serum vitamin B12 level.

Topics: Adult; Anemia, Megaloblastic; Female; Homocysteine; Humans; Neurodegenerative Diseases; Pancytopenia; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Animals; Biomarkers; Dietary Supplements; Disease Models, Animal; Folic Acid; Folic Acid Deficiency; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adult; Aged; Anemia, Megaloblastic; Erythrocyte Transfusion; Female; Humans; Iron; Iron Overload; Male; Transferrin; Vitamin B 12; Vitamin B 12 Deficiency

A nine-year-old girl without aggravating family history or adverse pregnancy and neonatal outcome, who underwent a resection of the end section of the small bowel as a result of atresia in the first twenty four hours of her life, was admitted to the Department on account of spastic paresis of the lower extremities. Apathy and tiredness appeared the most striking features on the physical examination of the child; likewise the pale colour of skin and a scar on the abdomen integuments--a result of the resection. Neurological examination revealed pyramidal syndrome from the lower extremities, disturbed sense of balance with intensified with closed eyes, and deep sensibility disorders. Megaloblastic anaemia was revealed on further examination, while bone marrow image showed normoblastic erythropoiesis with the presence of megaloid cells. The extremely low level of vitamin B12 in the blood serum and a regular level of folic acid were found. The vitamin B12 absorption test (Schilling test) showed considerable impairment in the process. The inflammation of the esophagus and duodenum mucosa was confirmed in a histopathological examination. Furthermore, irregular result of somatosensory induced potentials (SEP) and conductivity test revealed some characteristics of axonal--demyelinating neuropathy in the lower extremities. MRI of the head and spinal cord was correct. The diagnostics excluded methylomalonic acidosis, multiple sclerosis and other causes of ataxia in children. The overall clinical picture, that is megaloblastic anaemia, the characteristics of the myelosis funicularis and interview data--resection of the bowel as well as other examinations confirmed that the observed disorders resulted from the impairment of vitamin B12 absorption. An appropriate treatment consisted of supplementation of vitamin B12 (intramuscular) and folic acid (orally) improved the neurological condition and hematologic parameters.. It is necessary to monitor hematologic parameters and the neurologic condition in the group of children who underwent the resection of the ileum in infancy. If vitamin B12 deficiency symptoms occur, appropriate treatment should be duly applied.

Topics: Anemia, Megaloblastic; Child; Female; Folic Acid Deficiency; Humans; Ileal Diseases; Infant; Intussusception; Malabsorption Syndromes; Primary Myelofibrosis; Vitamin B 12; Vitamin B 12 Deficiency

The cblE type of homocystinuria is a rare autosomal recessive disorder, which manifests with megaloblastic anaemia and developmental delay in early childhood. This disease is caused by a defect in reductive activation of methionine synthase (MTR). Our study was directed at clinical, biochemical, enzymatic and molecular characterization of two Czech patients with the cblE type of homocystinuria. Case 1 involves a 20-year-old mentally retarded patient who presented with megaloblastic anaemia at 10 weeks of age. She was treated with folates and vitamin B12, and subsequent attempts to cease administration of folates led to recurrence of megaloblastic anaemia. Biochemical features included severe hyperhomocysteinaemia and hypomethioninaemia and in fibroblasts defective formation of methionine from formate, and no complementation with cblE cells. Subsequent molecular analysis of the methionine synthase reductase (MTRR) gene revealed compound heterozygosity for a transition c.1459G>A (G487R) and a 2bp insertion (c.1623-1624insTA). Case 2 involves an 8-year-old girl with nystagmus and developmental delay in whom megaloblastic anaemia was detected at 11 weeks of age. Severe hyperhomocysteinaemia with normal methionine levels was found and enzymatic and complementation studies confirmed the cblE defect. This patient is homozygous for a 140 bp insertion (c.903-904ins140). The insertion is caused by a T>C transition within intron 6 of the MTRR gene, which presumably leads to activation of an exon splicing enhancer. In the families of both patients, enzymatic and mutation analyses were successfully used for prenatal diagnosis. Our study expands the knowledge of the phenotypic and genotypic variability of the cblE type of homocystinuria and supports the concept that this disorder is caused by mutations in the MTRR gene.

Topics: Adult; Anemia, Megaloblastic; Base Sequence; Cells, Cultured; Child; Chromatography, Ion Exchange; DNA; Female; Ferredoxin-NADP Reductase; Fibroblasts; Folic Acid; Homocysteine; Homocystinuria; Humans; Methionine; Molecular Sequence Data; Mutation; Prenatal Diagnosis; Reverse Transcriptase Polymerase Chain Reaction; Serine; Vitamin B 12

We present a case of extreme pancytopenia in a 27-year-old pregnant woman. The initial picture was compatible with a severe hematological problem in the category of aplastic anemia, paroxysmal nocturnal hemoglobinuria or even acute leukemia. The further biochemical investigations revealed, however, a folate deficiency. Nowadays this is a very rare cause of pancytopenia. Next to this she also had a Vitamin B(12) deficiency due to intrinsic factor failure. The recent literature is discussed.

Topics: Adult; Anemia, Megaloblastic; Blood Transfusion; Bone Marrow; Female; Folic Acid; Folic Acid Deficiency; Humans; Infant, Newborn; Intrinsic Factor; Male; Pancytopenia; Platelet Transfusion; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Vitamin B 12; Vitamin B 12 Deficiency

This article presents the case of a 46-year-old vegetarian who had a painful dry socket in the left third molar areas. Since the patient's general appraisal was anaemic, investigations for haematological status, folic acid and vitamin B12 were performed. The results revealed that the patient was severely iron deficient and slightly vitamin B12 deficient.

Topics: Anemia, Iron-Deficiency; Anemia, Megaloblastic; Diet, Vegetarian; Dry Socket; Enzyme-Linked Immunosorbent Assay; Female; Ferritins; Folic Acid; Folic Acid Deficiency; Humans; Middle Aged; Radioimmunoassay; Thailand; Vitamin B 12; Vitamin B 12 Deficiency

The treatment of acquired cobalamin deficiency in infants may result in the development of a syndrome defined by temporary involuntary myoclonic movements. A patient with an inborn error of metabolism resulting in transcobalamin 2 deficiency who was treated with cobalamin and then developed this syndrome is presented. Neurologic investigations were normal. The continuance of cobalamin and avoidance of antiepileptic drugs is recommended. To our knowledge this is the first such case.

Topics: Anemia, Megaloblastic; Chromosome Aberrations; Chromosome Disorders; Diagnosis, Differential; Genes, Recessive; Genetic Carrier Screening; Humans; Infant; Male; Myoclonus; Transcobalamins; Vitamin B 12

We have previously demonstrated that vitamin B12 (cobalamin)-deficient central neuropathy in the rat is associated with local overexpression of neurotoxic tumour necrosis factor (TNF)-alpha combined with locally decreased synthesis of neurotrophic epidermal growth factor (EGF). The aims of this study were to investigate whether a similar imbalance also occurs in the serum of adult patients with clinically confirmed cobalamin deficiency and whether it can be corrected by vitamin B12 replacement therapy.. We studied 34 adult patients with severe cobalamin deficiency, 12 patients with pure iron deficiency anaemia and 34 control subjects. Haematological markers of cobalamin deficiency and serum TNF-alpha and EGF levels were measured using commercial kits. Thirteen cobalamin-deficient patients were re-evaluated after 3 and 6 months of parenteral vitamin B12 treatment.. TNF-alpha was significantly higher (p < 0.01) and EGF significantly lower (p < 0.01) in the patients with cobalamin deficiency, but both were unchanged in patients with pure iron deficiency anaemia. In cobalamin-deficient patients the serum TNF-alpha levels correlated significantly with plasma total homocysteine levels (r = 0.425; p < 0.02). In the treated patients TNF-alpha and EGF levels normalised concomitantly with clinical and haematological disease remission.. In humans, as in rats, cobalamin concentration appears to be correlated with the synthesis and release of TNF-alpha and EGF in a reciprocal manner, because cobalamin deficiency is accompanied by overproduction of TNF-alpha and underproduction of EGF.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Hypochromic; Anemia, Megaloblastic; Animals; Bone Marrow; Epidermal Growth Factor; Female; Folic Acid; Follow-Up Studies; Gastritis, Atrophic; Homocysteine; Humans; Iron; Iron Deficiencies; Male; Middle Aged; Peripheral Nervous System Diseases; Rats; Species Specificity; Tumor Necrosis Factor-alpha; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Megaloblastic; Anesthetics; Humans; Malabsorption Syndromes; Mass Screening; Nitrous Oxide; Preoperative Care; Spinal Cord Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adult; Anemia, Megaloblastic; Folic Acid; Folic Acid Deficiency; Homocystinuria; Humans; Male; Vitamin B 12; Vitamin B 12 Deficiency

Elevation of mean cell volume (MCV) is a common clinical problem, but the etiologic spectrum and optimal diagnostic evaluation of macrocytosis are not well defined.. We studied 300 consecutive hospitalized adult patients with MCV values > or = 100 fL. Assessment included complete blood counts, morphologic review, liver function tests, and levels of serum cobalamin (Cbl), methylmalonic acid, and total homocysteine.. The most common cause of macrocytosis was drug therapy, followed by alcohol, liver disease, and reticulocytosis. Megaloblastic hematopoiesis accounted for less than 10% of cases. MCV values > 120 fL were usually caused by Cbl deficiency. Anisocytosis, macro-ovalocytosis, and teardrop erythrocytes were most prominent in megaloblastic hematopoiesis. Elevated levels of serum methylmalonic acid and total homocysteine were useful in the diagnosis of Cbl deficiency.. Drugs and alcohol are the most common causes of macrocytosis in hospitalized patients in a New York City teaching hospital. We have formulated tentative guidelines for the evaluation of high MCV values in this setting.

Topics: Adult; Aged; Alcohol Drinking; Anemia, Macrocytic; Anemia, Megaloblastic; Bone Marrow Diseases; Diagnosis, Differential; Drug-Related Side Effects and Adverse Reactions; Female; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; L-Lactate Dehydrogenase; Leukocyte Count; Liver Diseases; Liver Diseases, Alcoholic; Male; Methylmalonic Acid; Middle Aged; Platelet Count; Predictive Value of Tests; Prospective Studies; Reticulocyte Count; Sensitivity and Specificity; Vitamin B 12; Vitamin B 12 Deficiency

Megaloblastic anemia 1 (MGA1) is an autosomal recessive disorder caused by the selective intestinal malabsorption of intrinsic factor (IF) and vitamin B(12)/cobalamin (Cbl) in complex. Most Finnish patients with MGA1 carry the disease-specific P1297L mutation (FM1) in the IF-B(12) receptor, cubilin. By site-directed mutagenesis, mammalian expression, and functional comparison of the purified wild-type and FM1 mutant forms of the IF-Cbl-binding cubilin region (CUB domains 5-8, amino acid 928-1386), we have investigated the functional implications of the P1297L mutation. Surface plasmon resonance analysis revealed that the P1297L substitution specifically increases the K(d) for IF-Cbl binding several-fold, largely by decreasing the association rate constant. In agreement with the binding data, the wild-type protein, but not the FM1 mutant protein, potently inhibits 37 degrees C uptake of iodine 125-IF-Cbl in cubilin-expressing epithelial cells. In conclusion, the data presented show a substantial loss in affinity of the FM1 mutant form of the IF-Cbl binding region of cubilin. This now explains the malabsorption of Cbl and Cbl-dependent anemia in MGA1 patients with the FM1 mutation. (Blood. 2000;96:405-409)

Topics: Anemia, Megaloblastic; Binding Sites; Cloning, Molecular; Gene Expression; Humans; Intrinsic Factor; Membrane Glycoproteins; Mutagenesis, Site-Directed; Mutation; Polymerase Chain Reaction; Receptors, Cell Surface; Structure-Activity Relationship; Surface Plasmon Resonance; Transfection; Vitamin B 12

Deficiency of folate or vitamin B(12) (cobalamin) causes megaloblastic anemia, a disease characterized by pancytopenia due to the excessive apoptosis of hematopoietic progenitor cells. Clinical and experimental studies of megaloblastic anemia have demonstrated an impairment of DNA synthesis and repair in hematopoietic cells that is manifested by an increased percentage of cells in the DNA synthesis phase (S phase) of the cell cycle, compared with normal hematopoietic cells. Both folate and cobalamin are required for normal de novo synthesis of thymidylate and purines. However, previous studies of impaired DNA synthesis and repair in megaloblastic anemia have concerned mainly the decreased intracellular levels of thymidylate and its effects on nucleotide pools and misincorporation of uracil into DNA. An in vitro model of folate-deficient erythropoiesis was used to study the relationship between the S-phase accumulation and apoptosis in megaloblastic anemia. The results indicate that folate-deficient erythroblasts accumulate in and undergo apoptosis in the S phase when compared with control erythroblasts. Both the S-phase accumulation and the apoptosis were induced by folate deficiency in erythroblasts from p53 null mice. The complete reversal of the S-phase accumulation and apoptosis in folate-deficient erythroblasts required the exogenous provision of specific purines or purine nucleosides as well as thymidine. These results indicate that decreased de novo synthesis of purines plays as important a role as decreased de novo synthesis of thymidylate in the pathogenesis of megaloblastic anemia.

Topics: Anemia, Megaloblastic; Animals; Apoptosis; Cell Cycle; Cells, Cultured; DNA Repair; DNA Replication; Erythroblasts; Folic Acid; Genes, p53; Kinetics; Mice; Mice, Inbred Strains; Mice, Knockout; S Phase; Vitamin B 12

New hypotheses have recently been developed on vitamin B12 deficiency and the frequently observed occurrence in the elderly subject of food cobalamin malabsorption, i.e., the non-dissociation of B12 and its carrier protein (ND B12), and the possibility of rectifying this imbalance by oral crystalline B12 supplementation. The aim of this study was therefore to confirm these hypotheses in a series of patients aged over 75 years with anemia due to B12 deficiency.. A retrospective study was carried out over a 5-year period on patients aged over 75 years presenting with megaloblastic anemia (hemoglobin [Hb] < 12 g/dL) and vitamin B12/cobalamin deficiency (B12 < 160 pg/mL).. Twenty cases were analyzed. The average age of the patient population was 82.5 +/- 6 years, and the F/M sex ratio was 1:2. Mean Hb levels were 7.9 +/- 2.4 g/dL, mean serum B12 levels were 83 +/- 24 pg/mL, and mean homocysteinemic levels were 35 +/- 27 mumol/L. The diagnosis was as follows: food cobalamin malabsorption/ND B12 (n = 10), Biermer's disease/pernicious anemia (n = 5), malabsorption due to pancreatic insufficiency (n = 1), and low dietary B12 levels (n = 1). Disorders associated with ND B12 were: atrophic gastritis and Helicobacter pylori infection (n = 6), antacid or biguanide intake (n = 3), alcohol abuse (n = 2), or idiopathic syndrome (n = 2). In the patients who were followed up (n = 10), i.m. (n = 5) or oral (n = 5) administration of crystalline B12 resulted in the correction of hematological abnormalities.. In the elderly subject, food cobalamin/ND B12 malabsorption appears to be the main cause of B12 deficiency, and is frequently associated with atrophic gastritis. In these cases, administration of oral crystalline B12 may be an efficient means of treating this disorder.

Topics: Aged; Aged, 80 and over; Anemia, Megaloblastic; Carrier Proteins; Female; Humans; Malabsorption Syndromes; Male; Retrospective Studies; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adolescent; Adult; Anemia, Megaloblastic; Child; Female; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Receptors, Cell Surface; Reference Values; Vitamin B 12

Methionine synthase reductase (MSR) deficiency is an autosomal recessive disorder of folate/cobalamin metabolism leading to hyperhomocysteinemia, hypo- methioninemia and megaloblastic anemia. Deficiency in MSR activity occurs as the result of a defect in the MSR enzyme, which is required for the reductive activation of methionine synthase (MS). MS itself is responsible for the folate/cobalamin-dependent conversion of homo- cysteine to methionine. We have recently cloned the cDNA corresponding to the MSR protein, a novel member of the ferredoxin-NADP(+)reductase (FNR) family of electron transferases. We have used RT-PCR, heteroduplex, single-strand conformation poly- morphism (SSCP) and DNA sequence analyses to reveal 11 mutations in eight patients from seven families belonging to the cblE complementation group of patients of cobalamin metabolism that is defective in the MSR protein. The mutations include splicing defects leading to large insertions or deletions, as well as a number of smaller deletions and point mutations. Apart from an intronic substitution found in two unrelated patients, the mutations appear singular among individuals. Of the eleven, three are nonsense mutations, allowing for the identification of two patients for whom little if any MSR protein should be produced. The remaining eight involve point mutations or in-frame disruptions of the coding sequence and are distributed throughout the coding region, including proposed FMN, FAD and NADPH binding sites. These data demonstrate a unique requirement for MSR in the reductive activation of MS.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Anemia, Megaloblastic; DNA Mutational Analysis; DNA, Complementary; Enzyme Activation; Ferredoxin-NADP Reductase; Folic Acid; Genes, Recessive; Genetic Complementation Test; Heteroduplex Analysis; Homocysteine; Humans; Hyperhomocysteinemia; Methionine; Mutation; Polymorphism, Single-Stranded Conformational; Reverse Transcriptase Polymerase Chain Reaction; RNA Splicing; Sequence Analysis, DNA; Vitamin B 12

An 18-month-old girl presented with macrocytic megaloblastic anaemia followed by haemolytic uraemic syndrome. Metabolic investigations led to the identification of an inborn error of cobalamin metabolism consisting of defective methylcobalamin biosynthesis, probably cobalamin G, since methionine synthase activity was decreased under standard reducing conditions. Despite treatment, pulmonary hypertension progressively developed and responded to oxygen therapy. Renal involvement evolved to terminal failure and haemodialysis, while pulmonary hypertension was controlled by oxygen therapy. Such clinical manifestations have never been reported in association with a defect of methylcobalamin and thus of methionine biosynthesis. A congenital abnormality of cobalamin metabolism was suspected then confirmed in the presence of typical haematological features associated with unusual clinical manifestations such as progressive renal failure and pulmonary hypertension.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Anemia, Megaloblastic; Female; Hemolytic-Uremic Syndrome; Humans; Hypertension, Pulmonary; Infant; Metabolism, Inborn Errors; Methionine; Vitamin B 12

Topics: Aged; Aged, 80 and over; Anemia, Megaloblastic; Drug Resistance; Epoetin Alfa; Erythrocyte Indices; Erythropoietin; Folic Acid; Hemoglobins; Humans; Male; Recombinant Proteins; Renal Dialysis; Vitamin B 12

To determine the diagnostic value of megaloblastic marrow in patients with possible vitamin B12 and/or folate deficiency and to look for criteria that could be used in diagnosis of vitamin B12 deficiency.. Prospective study.. Kenyatta National Hospital and M P Shah Hospital, Nairobi.. Patients of all age groups and both sexes presenting with clinical and blood picture of macrocytic anaemia.. Response to vitamin B12 injections. Vitamin B12 deficiency diagnosed by the following methods: Vitamin B12 serum level assays alone, bone marrow examination alone and both vitamin B12 assays and bone marrow examination. Response was measured clinically and by increase in haemoglobin level after three weeks of treatment.. Three hundred and forty-three patients were evaluated; 156 (45.5%) were males, and 187 (54.5%) females. Age range was 13-80 years and a mean of 37.7 years. Initial investigations were as follows: 21.9% had vitamin B12 assays only, 59.2% bone marrow examination only and 19.9% both vitamin B12 assayed and bone marrow evaluated. Haemoglobin increase after a total of 6,000 mcg of vitamin B12 was between 2.6-4.6 g/dl in three weeks. Reticulocytes measured on day ten ranged between 12% and 17%. Uniform improvement in all patients was observed for white blood cells (WBC) and platelet counts. Other significant results and observations included clinical improvement in the signs and symptoms of anaemia after the 6,000 mcg injection of vitamin B12 given over three weeks. Serum folic acid level was determined in 21% of cases and in all these it was normal.. The important practical points were response to vitamin B12 in all cases and the importance of re-assessing patients after a total of 6,000 mcg of vitamin B12. Folic acid deficiency was not detected. Patients in these two institutions with megaloblastic anaemia had vitamin B12 deficiency. It is proposed that a model consisting of oval macrocytosis on blood film and megablastic bone marrow be treated with vitamin B12 injections in settings where vitamin B12 serum level assays are not easily available.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia, Macrocytic; Anemia, Megaloblastic; Bone Marrow Examination; Diagnosis, Differential; Female; Folic Acid; Folic Acid Deficiency; Hospitals, Urban; Humans; Kenya; Male; Middle Aged; Prospective Studies; Reproducibility of Results; Vitamin B 12; Vitamin B 12 Deficiency

Gräsbeck-Imerslund disease (congenital familial selective vitamin B12-malabsorption with proteinuria, MGA1, MIM No. 261100) is a rare disorder displaying autosomal recessive inheritance. This study was designed to investigate the usefulness of measuring the activity of the urinary receptor for the intrinsic factor-cobalamin complex as a tool to diagnose this disease.. The receptor activity was measured by a radioisotope-binding assay, using phenyl-Sepharose gel as the adsorbant solid phase of the receptor.. In 10 Finnish patients, urinary receptor activity was on the average 640 times (15-1400 times) lower than that in 13 healthy control subjects: mean values of 0.1 nmol/mol (range, 0.01-0.32 nmol/mol) and 6.4 nmol/mol (range, 3.8-12.4 nmol/mol) creatinine, respectively. The mean value of urinary receptor activity in 11 first-degree, healthy relatives of the patients was 4.6 nmol/mol (range, 1.1-10.4 nmol/mol) creatinine, a difference from levels in control subjects that is not statistically significant. When the first-degree relatives were divided into heterozygotes (parents and siblings heterozygous for the haplotype of genetic markers associated with the disease gene) and wild-type homozygotes (siblings not displaying the disease haplotype), no difference was seen.. Determination of receptor activity in the urine is a highly accurate method for diagnosis of Gräsbeck-Imerslund disease at an early stage, but it does not detect carriers of the disorder.

Topics: Absorption; Adult; Aged; Anemia, Megaloblastic; Finland; Heterozygote; Humans; Middle Aged; Proteinuria; Radioligand Assay; Receptors, Cell Surface; Vitamin B 12; Vitamin B 12 Deficiency

Serum erythropoietin (sEpo) concentration is primarily related to the rate of renal production and, under the stimulus of hypoxia, increases exponentially as hemoglobin (Hb) decreases. Additional factors, however, appear to influence sEpo, and in this work, we performed studies to evaluate the role of the red blood cell precursor mass. We first compared the relationship of sEpo with Hb in patients with low versus high erythroid activity. The first group included 27 patients with erythroid aplasia or hypoplasia having serum transferrin receptor (sTfR) levels < 3 mg/L (erythroid activity < 0.6 times normal), while the second one included 28 patients with beta-thalassemia intermedia having sTfR levels > 10 mg/L (erythroid activity > 2 times normal). There was no difference between the two groups with respect to Hb (8.3 +/- 1.6 v 8.0 +/- 1.3 g/dL, P > .05), but sEpo levels were notably higher in patients with low erythroid activity (1,601 +/- 1,542 v 235 +/- 143 mU/mL, P < . 001). In fact, multivariate analysis of variance (ANOVA) showed that, at any given Hb level, sEpo was higher in patients with low erythroid activity (P < .0001). Twenty patients undergoing allogeneic or autologous bone marrow transplantation (BMT) were then investigated. A marked increase in sEpo was seen in all cases at the time of marrow aplasia, disproportionately high when compared with the small decrease in Hb level. Sequential studies were also performed in five patients with iron deficiency anemia undergoing intravenous (IV) iron therapy. Within 24 to 72 hours after starting iron treatment, marked decreases in sEpo (up to one log magnitude) were found before any change in Hb level. Similar observations were made in patients with megaloblastic anemia and in a case of pure red blood cell aplasia. These findings point to an inverse relationship between red blood cell precursor mass and sEpo: at any given Hb level, the higher the number of red blood cell precursors, the lower the sEpo concentration. The most likely explanation for this is that sEpo levels are regulated not only by the rate of renal production, but also by the rate of utilization by erythroid cells.

Topics: Anemia; Anemia, Aplastic; Anemia, Hypochromic; Anemia, Megaloblastic; Antineoplastic Combined Chemotherapy Protocols; beta-Thalassemia; Bone Marrow Transplantation; Erythrocyte Indices; Erythroid Precursor Cells; Erythropoiesis; Erythropoietin; Feedback; Folic Acid; Hodgkin Disease; Humans; Iron; Kidney; Receptors, Transferrin; Transplantation Conditioning; Vitamin B 12

Topics: Administration, Oral; Anemia, Megaloblastic; Hematinics; Humans; Injections, Intramuscular; Vitamin B 12

Uptake of vitamin B12 (cyanocobalamin) is facilitated by the cobalamin-binder gastric intrinsic factor (IF), which recognizes a 460-kD receptor, cubilin, present in the epithelium of intestine and kidney. Surface plasmon resonance analysis of ligand-affinity-purified human cubilin demonstrated a high-affinity calcium- and cobalamin-dependent binding of IF-cobalamin. Complete cDNA cloning of the human receptor showed a 3597 amino acid peripheral membrane protein with 69% identity to rat cubilin. Amino-terminal sequencing of the receptor indicates that the cDNA sequence encodes a precursor protein undergoing proteolytic processing due to cleavage at a recognition site (Arg7-Glu8-Lys9-Arg) for the trans-Golgi proteinase furin. Using fluorescence in situ hybridization, radiation hybrid mapping, and screening of YAC clones, the human cubilin gene was mapped between the markers D10S1661 and WI-5445 on the short arm of chromosome 10. This is within the autosomal recessive megaloblastic anemia (MGA1) 6-cM region harboring the unknown recessive-gene locus of juvenile megaloblastic anemia caused by intestinal malabsorption of cobalamin (Imerslund-Gräsbeck's disease). In conclusion, the present molecular and genetic information on human cubilin now provides circumstantial evidence that an impaired synthesis, processing, or ligand binding of cubilin is the molecular background of this hereditary form of megaloblastic anemia.

Topics: Amino Acid Sequence; Anemia, Megaloblastic; Animals; Chromosome Mapping; Chromosomes, Artificial, Yeast; Chromosomes, Human, Pair 10; DNA, Complementary; Furin; Genes; Genes, Recessive; Humans; Hybrid Cells; In Situ Hybridization, Fluorescence; Intrinsic Factor; Kidney Cortex; Molecular Sequence Data; Polymerase Chain Reaction; Rats; Receptors, Cell Surface; Sequence Homology, Amino Acid; Species Specificity; Subtilisins; Swine; Vitamin B 12

We investigated the haematological effects of a massive dose of oral cobalamin (vitamin B12) on patients with cobalamin deficiency anaemia who had severe anaemia with a few neurological impairments and found that oral treatment was almost as effective as conventional injection therapy. The recovery of haematological indices with oral cobalamin preparations was slightly slower than with parenteral preparations, although the subjective symptoms disappeared soon after the start of therapy. The results of this study indicate that oral treatment keeps the cobalamin body stores satisfactorily filled and might be useful for older patients in whom injecting might be difficult.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anemia, Megaloblastic; Erythrocyte Count; Erythrocyte Indices; Female; Hematocrit; Hemoglobins; Humans; L-Lactate Dehydrogenase; Male; Middle Aged; Platelet Count; Vitamin B 12

Topics: Aged; Anemia, Megaloblastic; Anemia, Pernicious; Clinical Trials as Topic; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Severity of Illness Index; Vitamin B 12; Vitamin B 12 Deficiency

Seven cases of total colonic aganglionosis were reviewed with a follow-up period of 10 to 26 years, focusing on the relationship between the length of aganglionic ileum and postoperative metabolic disorders. Pulled-through ileum ranged from 0 to 65 cm from the ileocecal valve, and suprapelvic side-to-side anastomosis was performed between the pulled-through ileum and 17 to 40 cm of aganglionic colon (left side and transverse colon, four; right side colon, one; no colonic patch, two). Hemoglobin level in three out of four patients with ileal involvement of more than 25 cm was below 11 g/dL (10.9, 7.7, 6.6 g/dL, respectively). Serum iron level was less than 30 micrograms/dL (27, 21, 20, 18 micrograms/dL, respectively) in four out of five patients with ileal involvement of more than 10 cm. Serum vitamin B12 level was below 100 (100, 46 pg/dL, respectively) in two patients whose pulled-through ileum was 45 cm and 65 cm, respectively from the ileocecal valve. One patient needs periodical parenteral iron therapy and one was treated as megaloblastic anemia. In the patients with ileal involvement of more than 25 cm, both weight and height for age are very low at less than the fifth percentile, except for one patient whose side patch was at the right colon. One patient still needs parenteral nutritional support. Severe iron deficiency anemia, low level of B12, and growth retardation are apparent in the patients with total colonic aganglionosis with ileal involvement. Colonic side-to-side anastomosis does not substitute for the loss of terminal ileum.

Topics: Anastomosis, Surgical; Anemia, Iron-Deficiency; Anemia, Megaloblastic; Body Height; Body Weight; Colon; Follow-Up Studies; Growth Disorders; Hemoglobins; Hirschsprung Disease; Humans; Ileal Diseases; Infant; Iron; Male; Parenteral Nutrition; Postoperative Complications; Vitamin B 12; Vitamin B 12 Deficiency

Vitamin B12 deficiency is known to be associated with signs of demyelination, usually in the spinal cord. Lack of vitamin B12 in the maternal diet during pregnancy has been shown to cause severe retardation of myelination in the nervous system. We report the case of a 14(1)/2-month-old child of strictly vegetarian parents who presented with severe psychomotor retardation. This severely hypotonic child had anemia due to insufficient maternal intake of vitamin B12 with associated megaloblastic anemia. MRI of the brain revealed severe brain atrophy with signs of retarded myelination, the frontal and temporal lobes being most severely affected. It was concluded that this myelination retardation was due to insufficient intake of vitamin B12 and vitamin B12 therapy was instituted. The patient responded well with improvement of clinical and imaging abnormalities. We stress the importance of MRI in the diagnosis and follow-up of patients with suspected diseases of myelination.

Topics: Anemia, Megaloblastic; Atrophy; Brain; Demyelinating Diseases; Diet, Vegetarian; Female; Follow-Up Studies; Frontal Lobe; Humans; Infant; Magnetic Resonance Imaging; Muscle Hypotonia; Myelin Sheath; Pregnancy; Prenatal Exposure Delayed Effects; Psychomotor Performance; Temporal Lobe; Vitamin B 12; Vitamin B 12 Deficiency

We reviewed six cases of infantile megaloblastosis secondary to maternal vitamin B12 deficiency, the most common cause of infantile megaloblastosis in our institution. Two patients had long-term neurological sequelae, with a further patient remaining abnormal but at short follow-up. In 50% of cases the mother was asymptomatic, with subtle or no peripheral blood abnormalities, having early pernicious anaemia. Any infant which fails to thrive, with progressive neurological deterioration and haematological cytopenias should have their vitamin B12 and folate status rapidly assessed. This is one of the few potentially reversible causes of failure to thrive and neurological deterioration. Early diagnosis and treatment may prevent significant long-term sequelae.

Topics: Anemia, Megaloblastic; Female; Follow-Up Studies; Humans; Infant; Male; Nutritional Physiological Phenomena; Vitamin B 12; Vitamin B 12 Deficiency

Over a period of about 6 weeks a 49-year-old woman developed increasing exercise-dependent dyspnoea. Her general practitioner had diagnosed marked megaloblastic anaemia and she was hospitalised for its further elucidation. She reported to have eaten or drunk nothing but sweets, potato chips, salty pretzels, lemonade, coffee and tea over the last 2 years. Alcohol intake had been reliably denied by her and outsiders. On admission she weighed 106 kg, her height was 167 cm, and she looked anaemic, had dyspnoea and a sinus tachycardia. There was no evidence of external or internal bleeding and the physical examination was otherwise unremarkable.. Laboratory tests showed a haemoglobin concentration of 4.7 g/dl, as well as marked folic and vitamin B12 deficiency. The food items taken by her contain practically no cobalamine and no folic acid. Gastroscopy revealed grade 1 reflux oesophagitis. Malabsorption being excluded (normal Schilling test, no demonstrable autoantibodies against parietal cells, no evidence of exocrine pancreatic insufficiency), the lack of both vitamins and the megaloblastic anaemia caused by it could be explained only by a deficient food intake over several years.. After administration of cobalamine (1 mg intramuscularly twice weekly for 6 weeks, then 300 micrograms daily by mouth for 4 weeks) and folic acid (5 mg twice daily for 10 weeks), as well as a well-balanced diet as prescribed by a dietician, reticulocyte and erythrocyte concentrations had quickly risen to normal at a follow-up examination 2 months later.. The case of an anaemia entirely caused by a deficient diet dearly illustrates the need of a well-balanced food intake even in adults.

Topics: Anemia, Megaloblastic; Diet; Energy Intake; Female; Folic Acid; Folic Acid Deficiency; Hemoglobins; Humans; Middle Aged; Nutritional Requirements; Vitamin B 12; Vitamin B 12 Deficiency

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Adult; Anemia, Megaloblastic; Brain Diseases; Homocystinuria; Humans; Male; Methionine; Vitamin B 12

Imerslund syndrome, a recessive autosomal disease, initially described by Imerslund and Grasbeck in 1960, associates megaloblastic anemia and proteinuria.. We report on six cases, studied in five different families. All patients (mean age: 3.5 years) had clinical symptoms of anemia, three had malabsorption, proteinuria was present in five, at the time of diagnosis. Hemogram and decreased serum vitamin B12 levels were consistent with the diagnosis in all cases. Intra-muscular injections of cyanocobalamine was instituted on a life-time basis and the long term prognosis is good.. The diagnosis should be evoked when the three typical features are present: macrocytic anemia, decreased serum B12 level and proteinuria. It will be confirmed by the bone marrow megaloblastic aspects and the Schilling test findings.

Topics: Anemia, Megaloblastic; Child; Child, Preschool; Hematinics; Humans; Infant; Proteinuria; Vitamin B 12

The diagnosis of megaloblastic anaemias caused by cobalamine or folate deficiency are still difficult. The dosage of these two substances help to differenciate between both carencies, but it is not determinant of any of them and is an expensive method. Homocisteinuria (HC), methylmalonuria (MMA) and formiminoglutamic acid (FIGLU) are cheap tests which could help in the differential diagnosis, if they are used properly. We report 62 patients to whom we made these test simultaneously. All of the patients received 10 micrograms of vit B12 and after 72 hours, 1 mg/day of folic acid (for 3 days). In both cases waiting for the increase of reticulocytyes up to 150 x 10(9)/L as a form of therapeutic test of diagnosis. By this simple way we have detected 97.9% of specificity for cobalamin deficiency of the MMA test, and only 4.2% for HC. This last test had increased its specificity up to 91.6% in association with the negative FIGLU test. We have also found a high specificity (92.3%) for FIGLU due to the detection of folate deficiency, in opposition with other authors who had described it as low as 50%. We have also compared the costs of the 3 tests with the dosage of cobalamine and folate, and we have found that the formers are 11 times less expensive than the last ones.

Topics: Adolescent; Adult; Algorithms; Anemia, Megaloblastic; Cost Control; Diagnosis, Differential; Diagnostic Tests, Routine; Female; Folic Acid; Folic Acid Deficiency; Formiminoglutamic Acid; Histidine; Homocysteine; Humans; Male; Methylmalonic Acid; Middle Aged; Predictive Value of Tests; Pregnancy; Pregnancy Complications, Hematologic; Reticulocyte Count; Retrospective Studies; Sensitivity and Specificity; Time Factors; Urinalysis; Vitamin B 12; Vitamin B 12 Deficiency

This first detailed report of a female patient with functional methionine synthase deficiency due to the cblE defect describes treatment with several vitamins and cofactors and clinical progress for 17 years. Before treatment, major findings were microcephaly, psychomotor retardation, episodic reduced consciousness, megaloblastic anaemia, increased plasma free homocystine (> 20 mumol/L), low plasma methionine (< 10 mumol/L) and increased excretion of formiminoglutamate. On high-dose folic acid, biochemical abnormalities such as formiminoglutamate excretion and homocystinuria nearly normalized, but clinical and haematological abnormalities remained. On replacement of folate with methylcobalamin, alertness, motor function, speech and the electroencephalogram improved, biochemical features were similar, but the mean corpuscular volume increased. The best control was observed on a combination of folate and methylcobalamin. At 17 years of age she remains severely mentally retarded. In cultured fibroblasts methionine synthesis was reduced (0.03 nmol/mg/per 16 h, controls 2.4-6.9); methionine synthase activity was normal under high reducing conditions but decreased on limiting the reducing agent, dithiothreitol, to 5 mmol/L (18% of total, controls 51-81%); formation of methylcobalamin was low (4.5% of total cobalamins, control 57.5%) and complementation studies indicated the cblE defect. Methionine formation showed only minor increases in cells grown in folate- or cobalamin-supplemented medium. Serine synthesis, which was low in normal medium, increased with cobalamin supplementation. These studies suggest further heterogeneity within cblE mutants, show the difficulty of establishing the enzyme defect in vitro, and indicate a role for folate in addition to cobalamin in treatment.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Anemia, Megaloblastic; Erythrocyte Indices; Female; Fibroblasts; Folic Acid; Homocystinuria; Humans; Infant; Vitamin B 12

We report findings on a child presenting with neonatal homocystinuria, hypomethioninaemia and severe neurological symptoms, including developmental delay and seizures. Methylmalonic aciduria was not present. The activity of methionine synthase in fibroblasts was severely deficient and formation of methylcobalamin from 57Co labelled cyanocobalamin was very low. The patients cells complemented with those of a cblE patient but not with those of two cblG patients. No biochemical or clinical response to injections of hydroxycobalamin was found. Both off treatment and on betaine and methionine supplementation the patient, at age 8 years, has not developed megaloblastic anaemia. In addition, the patient is homozygous for the C677T polymorphism in the 5,10 methylenetetrahydrofolate reductase (MTHFR) gene and the concomitant existence of this mutation with the methionine synthase defect may prevent folate <> and thus anaemia.. We report the lack of megaloblastic anaemia in a patient with severe methionine synthase deficiency who is also homozygous for C677T in MTHFR, hypothesize that the MTHFR polymorphism protects the patient against anaemia and speculate that homozygosity for MTHFR C677T could cause the dissociation between haematological and neurological disease seen in some patients with vitamin B12 deficiency.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Anemia, Megaloblastic; Child; Child, Preschool; Homocystinuria; Homozygote; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Oxidoreductases Acting on CH-NH Group Donors; Polymorphism, Genetic; Vitamin B 12

Pattern shift visual evoked responses (PSVER) were studied in thirty patients suffering from severe megaloblastic anemia (mean Hb level was 4.25 +/- 1.22 g/dL) of nutritional origin. All patients lacked clinical stigmata of visual and neurologic impairment. Mean P100 latency in thirty age and sex matched controls was 96.35 +/- 6.75 ms (range 86-108 ms) and mean amplitude was 10.37 +/- 3.88 microV (range 4.8-20.8 microV). Mean P100 latency in megaloblastic anemia was 114.77 +/- 11.68 (range 91-142) ms, P < 001 vs. control) and mean amplitude was 8.85 +/- 2.8 microV (range 5.1-16.2 microV). Seventy percent cases had prolonged latency of P 100. After correction of anemia with therapeutic doses of vitamin B12 and folic acid in three months (mean Hb level was 12.08 +/- 1.86 g/dL), the mean P100 latency was 105.13 +/- 9.30 ms (range 92-121 ms P < 0.001 vs. controls) and mean amplitude was 10.72 +/- 4.13 microV (range 5.1-21.4 microV). There was significant improvement in P100 latency after correction of anemia (P < 0.01). There was a negative correlation between P100 latency and hemoglobin levels, though it was statistically not significant.

Topics: Adolescent; Adult; Aged; Anemia, Megaloblastic; Bone Marrow; Evoked Potentials, Visual; Female; Hematinics; Humans; Male; Middle Aged; Vitamin B 12

The deoxyuridine suppression test (dUST) was used to evaluate human immunodeficiency virus type 1 positive (HIV-1) patients with low serum levels of vitamin B12 and/or low red cell folate and to assess any possible interferences of azydothymidine (AZT) in this test. The dUST was studied in 29 HIV-1 positive patients, 18 without low serum vitamin B12 or low red cell folate and 11 with low serum vitamin B12 (6 patients), low red cell folate (4 patients) and 1 case with both. The role of AZT was studied using different concentrations (0.2, 2.5 and 10 microM/ml) in 2 groups: 1 group of 5 patients with vitamin B12 and/or folate deficiency and another group consisting of 13 healthy subjects. Methotrexate (MTX)(50 micrograms/ml) was added to induce a folate megaloblastic pattern in the latter group. Results of the dUST in the HIV-1 group without low levels of serum vitamin B12 fell within the health-related reference interval values. A vitamin B12 deficiency was only detected in 1 case in the HIV-1 group with low serum vitamin B12, although a folate deficiency pattern was observed in the 4 patients with low red cell folate. In the healthy subjects AZT induced a dose-dependent decrease of the MTX-induced folate megaloblastic pattern. The pattern was also observed in the group of patients with vitamin B12 or folate deficiency, although AZT did not entirely interfere with the dUST. The effect of AZT on the dUST was attributed to a decrease in the incorporation of the isotope in the absence of deoxyuridine. The dUST is useful in differentiating vitamin B12 deficient patients from HIV-1 infected patients with low levels of serum vitamin B12.

Topics: Anemia, Megaloblastic; Bone Marrow; Cells, Cultured; Deoxyuridine; Folic Acid; HIV Infections; HIV-1; Humans; Intestinal Absorption; Methotrexate; Vitamin B 12; Vitamin B 12 Deficiency; Zidovudine

The first case of cobalamin deficiency with megaloblastic anaemia in a patient under long-term omeprazole therapy is presented. This patient received omeprazole at a daily dose of 40-60 mg for 4 years as treatment for a gastro-oesophagal reflux complicated by peptic oesophagitis. Seric vitamin B12 was dramatically decreased at 80 pmol L-1. The Schilling test was normal (13%) with crystalline [57Co] cobalamin and it was at 0% with [57Co] cobalamin-labelled trout meat. All other assimilation tests were normal except an expiratory hydrogen breath test performed with lactulose. The haematological status was restored after intramuscular treatment with cobalamin. In conclusion, prolonged omeprazole therapy can be responsible for a cobalamin deficiency due to protein-bound cobalamin malabsorption.

Topics: Anemia, Megaloblastic; Enzyme Inhibitors; Gastroesophageal Reflux; Hematinics; Humans; Malabsorption Syndromes; Male; Middle Aged; Omeprazole; Schilling Test; Vitamin B 12; Vitamin B 12 Deficiency

Juvenile megaloblastic anemia caused by selective intestinal malabsorption of vitamin B12 has been considered a distinct condition displaying autosomal recessive inheritance. It appears to have a worldwide distribution, and comparatively high incidences were reported 30 years ago in Finland and Norway. More recently, the Mendelian inheritance of the condition has been questioned because almost no new cases have occurred in these populations. Here we report linkage studies assigning a recessive-gene locus for the disease to chromosome 10 in previously diagnosed multiplex families from Finland and Norway, proving the Mendelian mode of inheritance. The locus is tentatively assigned to the 6-cM interval between markers D10S548 and D10S466, with a multipoint maximum lod score (Zmax) of 5.36 near marker D10S1477. By haplotype analysis, the healthy sibs in these families did not appear to constitute any examples of nonpenetrance. We hypothesize that the paucity of new cases in these populations is due either to a dietary effect on the gene penetrance that has changed with time, or to a drop in the birth rate in subpopulations showing enrichment of the mutation, or to both of these causes.

Topics: Adolescent; Adult; Anemia, Megaloblastic; Child; Child, Preschool; Chromosome Mapping; Chromosomes, Human, Pair 10; Female; Genetic Linkage; Humans; Infant; Intestinal Absorption; Malabsorption Syndromes; Male; Middle Aged; Pedigree; Vitamin B 12

Neurologic damage may become permanent when the disorder is mistaken for multiple sclerosis or diabetic neuropathy--hence the need for prompt parenteral B12 in patients with pernicious anemia. The need for B12 injections is questionable for patients with achlorhydria and for those with a marginal or low serum B12 level but no signs or symptoms of deficiency.

Topics: Achlorhydria; Aged; Aged, 80 and over; Anemia, Megaloblastic; Anemia, Pernicious; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Neurologic Examination; Peripheral Nervous System Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adolescent; Adult; Aged; Anemia, Megaloblastic; Child; Child, Preschool; Female; Folic Acid; Humans; Infant; Male; Middle Aged; Pakistan; Reference Values; Social Class; Vitamin B 12; Vitamin B 12 Deficiency

A 22-month old boy with the congenital form of megaloblastic anaemia is presented. The child was admitted to hospital with moderate-to-severe hematological and neurological symptoms. Very low serum vitamin B12 concentration and normal gastric secretion were determined. A dramatic recovery after intramuscular injections with vitamin B12 was observed.

Topics: Anemia, Megaloblastic; Humans; Infant; Injections, Intramuscular; Male; Remission Induction; Vitamin B 12

The Imerslund-Gräsbeck syndrome (IGS) is a rare inherited disorder characterized by a megaloblastic anemia due to a selective vitamin B12 malabsorption in association with a mild proteinuria. Usually recurrent infections, gastrointestinal complaints, and pallor are presenting symptoms. We report two cases of IGS with an unusual presentation.. Two girls are described with the Imerslund-Gräsbeck syndrome who had a failure to thrive as a presenting symptom without infections or gastrointestinal complaints. The diagnosis of IGS was based on marked macrocytic anemia, very low serum vitamin B12 levels, abnormal Schilling urinary excretion test results, and mild proteinuria. When parenteral vitamin B12 was started, a rapid catch-up growth was seen in both girls.. The absence of well-known causes of failure to thrive, such as recurrent infections and gastrointestinal complaints, favors the concept that the metabolic disturbances caused by an isolated cobalamin deficiency as seen in IGS causes a failure to thrive.

Topics: Anemia, Megaloblastic; Failure to Thrive; Female; Humans; Infant; Proteinuria; Syndrome; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adult; Aged; Anemia, Megaloblastic; Erythrocyte Count; Erythropoiesis; Erythropoietin; Female; Folic Acid; Humans; Male; Middle Aged; Radioimmunoassay; Reticulocyte Count; Reticulocytes; Vitamin B 12

Imerslund-Najman-Grasbeck disease is a rare inherited megaloblastic anaemia secondary to a selective malabsorption of vitamin B12 by ileal enterocytes. The authors report on a 4 year-old tunisian girl who presented as visceral infantile leishmaniasis because of huge splenomegaly and major anaemia. The diagnosis of Imerslund disease was performed on the basis of the association of typical megaloblastic cells in the marrow, permanent proteinuria and favourable outcome under parenteral B12 administration. In addition, ther were no folate deficiency, no anti-intrinsic factor antibodies and no intrinsic factor deficiency. The outcome of the disease is always favourable if parenteral administration of vitamin B12 maintained.

Topics: Anemia, Megaloblastic; Child, Preschool; Female; Humans; Malabsorption Syndromes; Proteinuria; Vitamin B 12; Vitamin B 12 Deficiency

Macrocytic megaloblastic anemia is the most typical but the latest sign of a cobalamin (vitamin B12) and/or folic acid deficiency or of a congenital abnormality of cobalamin and folate metabolism. Macrocytosis in blood and megaloblastosis in bone marrow are the morphological features of a disturbance in cell division related to a defect in DNA biosynthesis. Macrocytosis without anemia, normocytic normochronic anemia with a low reticulocyte cell count or microcytic hypochromic anemia in case of associated iron deficiency do not exclude a vitamin deficiency. Neurological or psychiatric disorders and immune abnormalities have been reported in patients with vitamin B12 or folate deficiencies or in children with congenital abnormalities of these 2 vitamins; such manifestations may even occur without anemia.

Topics: Anemia, Megaloblastic; Diagnosis, Differential; Folic Acid; Humans; Metabolic Diseases; Transcobalamins; Vitamin B 12

Serum vitamin B12, folic acid and haematological variables of 132 Thai vegetarians (64 males and 68 females) were investigated. Forty-seven healthy omnivorous individuals served as controls. No statistical differences in haemoglobin concentration, packed red cell volume and mean corpuscular haemoglobin concentration between the vegetarians and controls had been detected. In the female vegetarians, the haemoglobin concentration and packed red cell volume were, however, statistically lower. No significant differences in the white cell counts and platelet counts were observed in both groups. A significant increase of basophilic stippling and reticulocytes was observed in the vegetarians. Serum vitamin B12 decreased and serum folic acid levels increased according to the duration of vegetarianism in the vegetarians. In the females practicing vegetarianism for 6-10 years or more, the proportion of serum vitamin B12 deficiencies was particularly high. The high percentage of vitamin B12 deficiency in the vegetarians might be related to megaloblastic anaemia. This form of anaemia is commonly associated with the presence of basophilic stippling. Therefore, the increased presence of basophilic stippling and reticulocytes might indicate a mild stage of this type of anaemia among the vegetarians.

Topics: Adult; Anemia, Megaloblastic; Basophils; Blood Cell Count; Diet, Vegetarian; Erythrocyte Indices; Female; Folic Acid; Hematocrit; Hemoglobins; Humans; Male; Middle Aged; Radioimmunoassay; Sex Factors; Thailand; Time Factors; Vitamin B 12; Vitamin B 12 Deficiency

The critical disturbance of folate metabolism caused by vitamin B12 deficiency which results in megaloblastic anaemia remains controversial. Vitamin B12 is required in the methionine synthase reaction in which homocysteine is converted to methionine and methyl tetrahydrofolate (methyl THF) to THF. The 'methyl-folate trap' hypothesis suggested that failure of demethylation of methyl THF with consequent deficiency of folate co-enzymes derived from THF is the crucial lesion caused by vitamin B12 deficiency. A more recent theory suggested that reduced supply of methionine leads to reduced availability of 'activated formate' and hence of formyl THF and it is this defect that results in failure of folate co-enzyme synthesis. The present results, based on deoxyuridine suppression tests on 103 cases of megaloblastic anaemia, show that THF itself is equally capable of correcting the failure of thymidylate synthesis in vitamin B12 deficiency as in folate deficiency. Although not as effective as formyl THF in correcting the dU blocking test in vitamin B12 deficiency, this is equally so for the correction of the test by THF compared with formyl THF in folate deficiency. The results therefore favour the theory that it is in the supply of THF and not of 'active formate' or formyl THF that vitamin B12 plays a critical role in folate metabolism.

Topics: Anemia, Megaloblastic; Bone Marrow; Cells, Cultured; Deoxyuridine; DNA; Female; Humans; Leucovorin; Male; Megaloblasts; Tetrahydrofolates; Thymidine Monophosphate; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Megaloblastic; Erythropoietin; Humans; Vitamin B 12

In order to further study the relation between transferrin receptor and erythropoiesis we examined serum receptor levels in megaloblastic anemia, which is the classic example of ineffective erythropoiesis. We studied 33 patients with unequivocal cobalamin deficiency, only 22 of whom were anemic. High serum transferrin receptor levels were found in 12 patients, all of whom were anemic and had high lactate dehydrogenase (LDH) levels; in contrast, only 10 of the 21 patients with normal receptor levels were anemic. Receptor correlated most strongly with LDH (r = 0.573, p < 0.001) and, inversely, with hemoglobin values (r = -0.560, p < 0.001); it also correlated with ferritin and total bilirubin levels, but not with cobalamin, MCV or erythropoietin. No association was found with the hemolytic component of megaloblastic anemia, represented indirectly by haptoglobin levels. Changes induced by cobalamin therapy were also examined in 13 patients. Transferrin receptors rose in all 6 patients who initially had high levels and in 2 of 3 patients who had borderline levels, but not in the 4 patients with initially normal levels. The receptor levels began to rise within 1-3 days, peaked at about 2 weeks and returned to normal at about the 5th wk. The findings indicate that serum transferrin receptor levels reflect the severity of the megaloblastic anemia. The elevated receptor levels rise further with cobalamin therapy, however, as effective erythropoiesis replaces ineffective erythropoiesis, and these persist until the increased erythropoiesis returns to normal.

Topics: Anemia, Megaloblastic; Bilirubin; Biomarkers; Blood Volume; Erythropoiesis; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; L-Lactate Dehydrogenase; Male; Middle Aged; Receptors, Transferrin; Transferrin; Vitamin B 12; Vitamin B 12 Deficiency

The authors present a case of Imerslund-Gräsbeck syndrome, i. e. a familial megaloblastic anemia with proteinuria. The disease is due to congenital, selective malabsorption of vitamin B12. The subnormal absorption of vitamin B12 is not altered by orally given intrinsic factor, but parenteral vitamin B12 therapy results in complete recovery. Approximately 150 cases have been described in literature, the authors' case is the first in Hungary.

Topics: Anemia, Megaloblastic; Child, Preschool; Female; Humans; Malabsorption Syndromes; Proteinuria; Syndrome; Vitamin B 12

Among 106 pregnant women with anaemia a typical state of iron deficiency could be shown at only 36.8%. 22.5% of the patients had a decreased vitamin B12 level without any characteristic symptoms of a megaloblastic anaemia. Predominantly the grade of the anaemia was small. The mean value of hemoglobin lied at 7.1 +/- 0.59 mmol/l. The severity of the anaemia didn't show any connection to the vitamin B12 level or parameters of the iron metabolism. With a combined therapy of iron, folic acid and vitamin B12 an increase of the Hb-level could be noticed at only 44.3% of the patients. The haematological findings, taken before the therapy, as well as the therapy results show that an important part of anaemias in pregnancy is caused by a complex genesis as a result of immunological reactions in pregnancy.

Topics: Adolescent; Adult; Anemia, Hypochromic; Anemia, Megaloblastic; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Ferrous Compounds; Folic Acid; Folic Acid Deficiency; Hemoglobinometry; Humans; Infant, Newborn; Iron; Pregnancy; Pregnancy Complications, Hematologic; Quaternary Ammonium Compounds; Vitamin B 12; Vitamin B 12 Deficiency

The case of a 59-year-old Japanese woman with post-gastrectomy megaloblastic anaemia having urinary and faecal incontinence and paraesthesia in four extremities is described. While the haematological abnormalities were improved by administration of a total dose of 17 mg of intramuscular mecobalamin, the neurological abnormalities remained unchanged. Five months later, a total dose of 7.5 mg of mecobalamin was injected intravenously over a period of 5 weeks, although the serum level of vitamin B12 was greater than 1180 pmol l-1. Immediately after initiation of the therapy, the urinary and faecal incontinence were gradually improved, and were completely cured within 2 months. The peripheral neuropathy was also ameliorated. The effectiveness of intravenous vitamin B12 injection for the neurological abnormalities due to vitamin B12 deficiency is emphasized.

Topics: Anemia, Megaloblastic; Fecal Incontinence; Gastrectomy; Humans; Injections, Intravenous; Male; Middle Aged; Urinary Incontinence; Vitamin B 12

A patient with post-gastrectomy megaloblastic anemia is described. Initially, the CD4/CD8 ratio of blood cells was abnormally high and the level of natural killer cell activity was markedly low. These abnormalities were, however, restored by vitamin B12 treatment. Taken together with our prior report on a patient with pernicious anemia in whom the decreased level of CD8-positive blood cells was corrected by vitamin B12 therapy, it may be considered that the reversible CD4/CD8 imbalance of blood cells noted in some cases of pernicious anemia is not pathognomonic for the disease but secondary to vitamin B12 deficiency.

Topics: Anemia, Megaloblastic; CD4-CD8 Ratio; Female; Gastrectomy; Humans; Killer Cells, Natural; Middle Aged; Vitamin B 12

The levels of serum folic acid and vitamin B12 were determined in 40 cases of liver cirrhosis with radioimmunoassay. It was shown that in 87.5% of the patients folic acid level was lower than that of a control group and in 67.5% serum vitamin B12 level was higher than that of the control group (P less than 0.05). The correlation between liver cirrhosis and dysbolism of folic acid and vitamin B12 and the megaloblastic changes and clinical significance were discussed.

Topics: Adult; Aged; Anemia, Megaloblastic; Female; Folic Acid; Humans; Liver Cirrhosis; Male; Middle Aged; Radioimmunoassay; Vitamin B 12

The case of a young woman from Guadeloupe developing severe megaloblastic anemia is reported. She presented with fever and hemolysis (she had heterozygotic beta-thalassemia) after a six month history of diarrhea. She was shown to have folate deficiency, steatorrhea, vitamin K and B12 malabsorption. She responded well to intravenous folinic acid and tetracyclines. Diagnosis was based on the following criteria: a) no other cause of malabsorption was found despite a comprehensive inquiry, b) the pattern of the illness corresponded to the definition of disease. Three particular aspects are outlined: the acute onset, malabsorption of vitamin B12 requiring prolonged and combined treatment, and the unusual place in which the disease was contracted.

Topics: Adult; Anemia, Megaloblastic; Drug Therapy, Combination; Female; Folic Acid; Folic Acid Deficiency; Humans; Infusions, Parenteral; Sprue, Tropical; Tetracycline; Thalassemia; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin K Deficiency; West Indies

In various anaemias the values of 8 acute phase factors were determined simultaneously before and at the end of treatment: seromucoid, sialic acid, acid alpha 1-glycoprotein, alpha 1-antitrypsin, haptoglobin, ceruloplasmin, transferrin and fibrinogen. In iron-deficiency anaemia without coexistent inflammatory changes in organs the levels of 4 proteins--seromucoid, alpha 1-antitrypsin, ceruloplasmin and transferrin, were consistently raised. In iron-deficiency anemia with concomitant infection 4 proteins also were increased, but in place of alpha 1-antitrypsin the haptoglobin level was raised. In megaloblastic anaemia the ceruloplasmin level was increased, and in haemolytic anaemia one factor--sialic acid--was decreased. At the end of treatment the concentrations of certain proteins were changed depending on their specific role in various forms of anaemia and on various additional factors. In iron-deficiency anaemia without coexistent infection the concentration of seromucoid was decreased, and in this anaemia with coexistent infection alpha 1-antitrypsin, haptoglobin, and fibrinogen levels were raised, in haemolytic anaemia only fibrinogen was increased, and megaloblastic anaemia was associated with raised seromucoid level. The therapeutic result was good in all these anaemias with the exception of iron-deficiency anaemia associated with infection in which it was less propitious.

Topics: Acute-Phase Proteins; Adolescent; Adult; Aged; Anemia; Anemia, Hemolytic, Autoimmune; Anemia, Hypochromic; Anemia, Megaloblastic; Anemia, Sideroblastic; Female; Glucocorticoids; Humans; Iron; Male; Middle Aged; Vitamin B 12

Imerslund-Gräsbeck syndrome, an autosomal recessive trait of defective uptake of intrinsic factor-vitamin B12 complex by terminal ileum, is described in a Saudi family (two siblings and their first cousin). This rare disease has previously been reported only in Northern Europe and North African Jewish ethnic groups.

Topics: Adolescent; Anemia, Megaloblastic; Child; Humans; Male; Pedigree; Saudi Arabia; Syndrome; Vitamin B 12; Vitamin B 12 Deficiency

A rare case of long-term bone marrow failure with skin pigmentation is presented. The patient was a female with a long history of anemia and skin pigmentation since childhood, although she had no malformations nor chromosomal abnormalities. Hematological improvement has been maintained by the administration of prednisolone. This case may differ from other disorders known as congenital aplastic anemia.

Topics: Addison Disease; Anemia, Megaloblastic; Anemia, Refractory; Child; Chromosome Aberrations; Fanconi Anemia; Female; Graves Disease; Hemochromatosis; Humans; Pancytopenia; Pigmentation Disorders; Skin Pigmentation; Steroids; Vitamin B 12

Topics: Anemia, Megaloblastic; Bone Marrow; Erythroid Precursor Cells; Female; Folic Acid; Hematopoietic Stem Cells; Humans; Hyperplasia; Middle Aged; Pancytopenia; Transcobalamins; Vitamin B 12

Topics: Adult; Anemia, Megaloblastic; Folic Acid; Humans; Vitamin B 12

Vitamin B12 malabsorption in the ileum has been postulated as the underlying cause of the Imerslund-Grasbeck syndrome comprising megaloblastic anemia, proteinuria, and multiple neurological abnormalities. A young Saudi child with spasticity, truncal ataxia, cerebral atrophy, megaloblastic anaemia and proteinuria is described. Replacement therapy with parenteral vitamin B12 resulted in the complete resolution of his neurological findings and brain atrophy.

Topics: Anemia, Megaloblastic; Atrophy; Brain Diseases; Cerebral Cortex; Child, Preschool; Humans; Male; Proteinuria; Syndrome; Tomography, X-Ray Computed; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adult; Aged; Anemia, Megaloblastic; Bone Marrow; Deoxyuridine; DNA; Female; Folic Acid; Humans; Male; Methylmalonic Acid; Middle Aged; Schilling Test; Vitamin B 12

Topics: Anemia, Hypochromic; Anemia, Megaloblastic; Female; Gastrectomy; Humans; Iron; Male; Vitamin B 12

Methylation of cytosine residues in DNA samples, collected before and serially after cobalamin treatment from patients with cobalamin deficiency, was studied using restriction endonucleases Hpa II and Msp I and an epsilon globin gene probe. There was no evidence of hypomethylation in any of the samples. It was concluded that although hypomethylation of metabolites such as choline occurs, that of DNA is preserved in megaloblastic anaemia.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Blotting, Southern; Deoxyribonuclease HpaII; Deoxyribonucleases, Type II Site-Specific; DNA; DNA Probes; Humans; Methylation; Vitamin B 12

Imerslund syndrome is a rare autosomal recessive disorder of megaloblastic anemia as a result of selective vitamin B12 malabsorption associated with proteinuria. An Arabic Muslim family is described, with three children who had inherited selective vitamin B12 malabsorption with proteinuria. Dolichocephaly was noted in all the male children of this family in association with congenital megaloblastic anemia and proteinuria. The findings of this anemia are compatible with Imerslund-Gräsbeck syndrome, and coexistence of this syndrome with dolichocephaly in a single family has not been previously reported.

Topics: Anemia, Megaloblastic; Consanguinity; Ethnicity; Female; Humans; Hypophosphatemia, Familial; Infant; Israel; Malabsorption Syndromes; Male; Proteinuria; Skull; Vitamin B 12; Vitamin B 12 Deficiency

A case of 78-year old man with megaloblastic anemia occurring 20 years after partial gastrectomy is reported. Since about 2 years earlier he had an episode of convulsion, and he had been on anti-convulsants (diphenylhydantion, phenobarbital) until admission. Physical examination revealed a pale lean man with polyneuropathy and mental impairment. Laboratory findings revealed WBC 3100/microliters, RBC 187 X 10(4)/microliters, HB 7.9 g/dl, MCV 124.4 microns3, MCH 42.7 micrograms, platelet counts 15.7 X 10(4)/microliters, serum vitamin B12 (VB12) 380 pg/ml, and serum folic acid 5.1 ng/ml. Serum autoantibodies to intrinsic factor (IF) and parietal cells were positive. Bone marrow examination revealed erythroid hyperplasia and megaloblastic changes. Schilling test revealed impaired absorption of VB12 with or without IF, but X-ray study of the small bowels was unremarkable. Treatment with intramuscular cyanocobalamin resulted in a rapid clinical improvement. A repeat Schilling test after 4 months of therapy showed a normal VB12 absorption in the presence of IF. These findings suggest that VB12 malabsorption of the 1st Schilling test was due to intestinal dysfunction caused by the VB12 deficiency state itself, and the improvement of VB12 absorption with IF after therapy suggests a pathogenesis similar to pernicious anemia in this patient.

Topics: Aged; Anemia, Macrocytic; Anemia, Megaloblastic; Autoantibodies; Gastrectomy; Humans; Intrinsic Factor; Male; Postoperative Complications; Schilling Test; Vitamin B 12

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Bone Marrow Cells; Deoxyuridine; DNA; Folic Acid; Folic Acid Deficiency; Humans; Schilling Test; Vitamin B 12; Vitamin B 12 Deficiency

The meaning of a low serum cobalamin level when the classic findings of pernicious anemia are lacking is undergoing reevaluation. We therefore studied the neurologic status of 11 patients who had low cobalamin levels without definite hematologic evidence of deficiency. Neurologic evaluation included pattern-shift visual and median and posterior tibial nerve somatosensory evoked potentials. None of the patients had megaloblastic changes in the blood or bone marrow, although 7 of the 11 had subtle cellular cobalamin disturbances demonstrated by an abnormal deoxyuridine suppression test result. Seven patients had normal Schilling test results and 2 had borderline results; however, 2 of the 5 patients tested further had food-cobalamin malabsorption, while a third had prepernicious anemia. The patients displayed a variety of neurologic problems, including dementia, depression, myelopathy, neuropathy, and seizure disorder; 1 patient was neurologically normal by clinical criteria. Evoked potential abnormalities were demonstrable in 8 of the 9 patients with subtle cobalamin deficiency, and in at least 5 cases the disturbance was central. In contrast, both patients whose low serum cobalamin levels were found on evaluation to be spurious had normal evoked potentials. Evoked potential abnormalities improved in the one patient retested after cobalamin therapy. These findings demonstrate that neurologic deficits occur not only in classic cobalamin deficiency but also in subtle or atypical cobalamin deficiency states in which anemia is absent and Schilling test results are normal. Electrophysiologic evidence of neurologic impairment is often present, even in patients without obvious clinical neurologic abnormalities.

Topics: Absorption; Adult; Aged; Anemia, Megaloblastic; Anemia, Pernicious; Evoked Potentials; Female; Humans; Intestinal Absorption; Male; Middle Aged; Nervous System Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Immerslund-Grasbeck syndrome is an uncommon disease, characterized by megaloblastic anaemia and persistent proteinuria. A Libyan boy with the characteristic findings is presented. He received intramuscular vitamin B12 injections and there followed a remarkable clinical and haematological improvement.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Child; Humans; Libya; Male; Proteinuria; Syndrome; Vitamin B 12

Cobalamin G mutation (cblG) typically presents as a severe megaloblastic anemia during the first few weeks of life. The anemia responds completely to treatment with high doses of Cbl but the neurologic manifestations respond more slowly and not always completely. Cultured fibroblasts from two affected infants and virus-transformed lymphoblasts from one of the infants expressed the following: poor growth in the absence of methionine, the ability to take up and internalize Cbl bound to transcobalamin II, impaired synthesis of methionine from homocysteine, the ability to bind incoming Cbl to the respective coenzymes, but an inability to synthesize methylcobalamin in spite of a normal capacity to synthesize adenosylcobalamin. The in vitro activity of the methyltransferase dependent on methylcobalamin of cell extracts varied from low to high depending on the conditions of culture and assay. The cblG cells were unusually sensitive to the concentration of adenosylmethionine in the assay. More adenosylmethionine was required by cblG cells to achieve the same level of enzyme activity as control cells and high concentrations of adenosylmethionine did not suppress activity as in control cells. It was postulated that the defect in cblG is in the metabolism of adenosylmethionine, an essential substance for the synthesis of methionine from homocysteine.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Anemia, Megaloblastic; Cell Division; Cells, Cultured; Female; Fibroblasts; Humans; Infant; Male; Methionine; Mutation; S-Adenosylmethionine; Transcobalamins; Vitamin B 12

The aim of this communication is to show the means by which free radicals could deleteriously alter the metabolism of cobalamin (vitamin B12) and iron in their attempt to protect the body against neoplasia or inflammation and in doing so, create the anaemia of chronic disease.

Topics: Anemia, Megaloblastic; Free Radicals; Humans; Iron; Nitrous Oxide; Vitamin B 12

Megaloblastic anaemia is very rare in the first weeks of life and it is related to impaired metabolism of folic acid or vitamin B12. One of this disorders is the congenital transcobalamin II deficiency. The case of a three month old infant, with vomiting, diarrhoea and severe anaemia is presented. Both parents and the child had very low or undetectable levels of serum TC II, respectively. Using i.m. hydroxycobalamin at high doses, the clinical and laboratory responses have been satisfactory.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Humans; Infant; Leucovorin; Male; Transcobalamins; Vitamin B 12

The laboratory findings of 20 patients with untreated megaloblastic anemia due to vitamin B12 deficiency were analysed. The material consists of 13 patients with pernicious anemia, 6 with postgastrectomy B12 deficiency and one with malabsorption syndrome. Hematological data (RBC, Hgb, Ht, WBC, Plt) were correlated with each other and serum LDH levels. Megaloblastic changes of bone marrow were apparent in cases of which Hgb values were below 9 g/dl, although its change were not clear in cases with mild anemia (above 9 g/dl). However, giant metamyelocytic changes of bone marrow were seen even in cases with mild anemia. Serum B12 levels in 6 out of 19 cases (31.6%) measured by clinical laboratory center were within normal range. In contrast, its level in all cases measured by radiodilution assay using R-protein or intrinsic factor were lower than normal values. Serum B12 levels measured by the latter method were correlated with various hematological data and also related with hematological severity, although its level measured by clinical laboratory did not have any correlation with hematological data. Schilling test seemed to be unreliable, because sample volume which was suggested by kit manual was too small (2 ml) to catch enough radioactivity for accurate measurement. Serum methylmalonic acid levels measured by gas capillary mass spectrophotometry were higher than normal values in all cases and were well correlated with hematological data.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Macrocytic; Anemia, Megaloblastic; Female; Humans; Male; Malonates; Methylmalonic Acid; Middle Aged; Predictive Value of Tests; Radioisotope Dilution Technique; Schilling Test; Spectrophotometry; Vitamin B 12; Vitamin B 12 Deficiency

Serum vitamin B12 levels were measured in 300 Indian subjects, comprising 165 haematologically normal volunteers, 78 cases of nutritional megaloblastic anaemia and 57 patients with myeloproliferative disorders. Each sample was assayed by three different techniques: i) a microbiological assay using Euglena gracilis as the test organism; ii) radioisotope dilution assay, using pure intrinsic factor as the B12 binder and haemoglobin-coated charcoal for separation of bound from free vitamin B12; iii) radioisotope dilution assay using intrinsic factor as the vitamin B12 binder and DEAE cellulose for separation of bound from free vitamin B12. Results by the three methods correlated closely at normal and high levels of serum B12: at low levels microbiological assay and radio-assay using haemoglobin-coated charcoal correlated well but DEAE cellulose failed to detect 16 of 68 patients with vitamin B12 deficiency. The radioisotope dilution assay tended to yield higher values of serum vitamin B12 than did the microbiological assay. In none of the healthy volunteers was a clearly low value found by any of the techniques, but 20 of them had low serum B12 levels. Radioisotope dilution assay using haemoglobin-coated charcoal is recommended as an accurate assay procedure for developing countries like India, where ready-made kits are not easily available and vitamin B12 deficiency states are common.

Topics: Anemia, Megaloblastic; DEAE-Cellulose; Evaluation Studies as Topic; Humans; India; Microbiological Techniques; Myeloproliferative Disorders; Radioisotope Dilution Technique; Vitamin B 12

We examined causes and hematological consequences of low serum cobalamin (vitamin B12) concentration in two representative population samples of 70-year-old (N = 293) and 75-year-old subjects (N = 486). Subjects with values below 130 pmol/liter (4.8% and 5.6%, respectively) were investigated with Schilling test, upper gastrointestinal endoscopy, determination of serum gastrin and group I pepsinogens, and bone marrow examination. Gastrointestinal abnormalities of etiologic significance were found in 26 of the 32 examined subjects: atrophy of the gastric body mucosa (N = 16, with pernicious anemia in six), partial gastrectomy (N = 6), and intestinal malabsorption (N = 4). Megaloblastic hematopoiesis was found in 10 individuals, four of whom had macrocytic anemia. Our results indicate that low serum cobalamin concentration in the elderly is usually a consequence of disease rather than of high age per se and that gastric mucosal atrophy is a major etiologic factor.

Topics: Aged; Aging; Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Bone Marrow Examination; Digestive System; Endoscopy; Female; Gastrins; Gastrointestinal Diseases; Humans; Male; Pepsinogens; Schilling Test; Vitamin B 12

A 40-year-old man who was resected ascending colon and terminal ileum (10 cm) in Aug. 1978, with the diagnosis of Crohn's disease, was admitted to our hospital with general fatigue, paresthesia and tremor in May. 1984. A peripheral blood examination on admission revealed Hb 10.1 g/dl, RBC 234 X 10(4)/mm3, MCV 131.4 fl, MCH 43.2 pg. A bone marrow specimen showed marked erythroid hyperplasia (W/E 1.44) with megaloblastic change. While serum folate level was normal, serum vitamin B12 value was low and Schilling test showed vitamin B12 malabsorption. Roentgenologic and endoscopic examinations revealed diffuse cobblestone appearances in small intestine (from anastomosis part to duodenal bulb). These examinations suggested vitamin B12 malabsorption with diffuse Crohn's disease caused megaloblastic anemia. The patient had been treated with vitamin B12 1,000 micrograms/day injection and, in Sep. 1984, he recovered from megaloblastic anemia (Hb 13.4 g/dl, RBC 440 X 10(4)/mm3, MCV 90.7 fl, MCH 30.4 pg).

Topics: Adult; Anemia, Macrocytic; Anemia, Megaloblastic; Crohn Disease; Humans; Intestinal Absorption; Malabsorption Syndromes; Male; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Megaloblastic; Bone Marrow; Deoxyuridine; Developmental Disabilities; Erythrocytes; Female; Folic Acid; Humans; Infant; Iron; Male; Syndrome; Transcobalamins; Tremor; Vitamin B 12; Vitamin B 12 Deficiency

Two Spanish siblings, a boy and girl, with transcobalamin II (TCII) deficiency are described. Both have grown and developed mentally normally after 10 years of vitamin B12 therapy. Two other siblings died soon after birth and it is almost certain that they also suffered from TCII deficiency.

Topics: Anemia, Megaloblastic; Child; Female; Follow-Up Studies; Humans; Male; Sibling Relations; Syndrome; Transcobalamins; Vitamin B 12

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Humans; Male; Middle Aged; Polycythemia Vera; Vitamin B 12

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Fibroblasts; Homocystinuria; Humans; Infant, Newborn; Male; Malonates; Methylmalonic Acid; Mutation; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Aged; Anemia, Macrocytic; Anemia, Megaloblastic; Female; Humans; Nitrous Oxide; Vitamin B 12

Topics: Adult; Anemia, Macrocytic; Anemia, Megaloblastic; Female; Humans; Male; Pedigree; Vitamin B 12

Among 141 consecutive patients with neuro-psychiatric abnormalities due to cobalamin deficiency, we found that 40 (28 percent) had no anemia or macrocytosis. The hematocrit was normal in 34, the mean cell volume was normal in 25, and both tests were normal in 19. Characteristic features in such patients included paresthesia, sensory loss, ataxia, dementia, and psychiatric disorders; longstanding neurologic symptoms without anemia; normal white-cell and platelet counts and serum bilirubin and lactate dehydrogenase levels; and markedly elevated serum concentrations of methylmalonic acid and total homocysteine. Serum cobalamin levels were above 150 pmol per liter (200 pg per milliliter) in 2 patients, between 75 and 150 pmol per liter (100 and 200 pg per milliliter) in 16, and below 75 pmol per liter (100 pg per milliliter) in only 22. Except for one patient who died during the first week of treatment, every patient in this group benefited from cobalamin therapy. Responses included improvement in neuropsychiatric abnormalities (39 of 39), improvement (often within the normal range) in one or more hematologic findings (36 of 39), and a decrease of more than 50 percent in levels of serum methylmalonic acid, total homocysteine, or both (31 of 31). We conclude that neuropsychiatric disorders due to cobalamin deficiency occur commonly in the absence of anemia or an elevated mean cell volume and that measurements of serum methylmalonic acid and total homocysteine both before and after treatment are useful in the diagnosis of these patients.

Topics: Adolescent; Adult; Aged; Anemia; Anemia, Megaloblastic; Ataxia; Erythrocyte Indices; Erythrocytes; Female; Hematocrit; Homocysteine; Humans; Hypesthesia; Iron; Male; Methylmalonic Acid; Middle Aged; Nervous System Diseases; Neurocognitive Disorders; Paresthesia; Vitamin B 12; Vitamin B 12 Deficiency

A number of patients with megaloblastic anemia and homocystinuria associated with low levels of methylcobalamin synthesis in cultured cells have been recognized. Methionine biosynthesis by intact cells, as determined by incorporation of label from 5-[14C]methyl-tetrahydrofolate into acid-precipitable material, was deficient in cultured skin fibroblasts that were derived from all of these patients. In one group of patients, activity of the methylcobalamin-dependent enzyme, methionine synthase, in cell extracts was within the normal range when the enzyme was assayed under standard conditions. In a second group of patients, methionine synthase activity was decreased under the same assay conditions. Genetic complementation analysis demonstrated the existence of two complementation classes that corresponded to these two groups of patients. The designation cblE has previously been proposed for normal methionine synthase activity. We propose the designation cblG for the mutation in those patients with methylcobalamin deficiency and decreased synthase activity. The results of these studies suggest that the products of at least two loci are required for cobalamin-dependent methionine biosynthesis in mammalian cells.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Anemia, Macrocytic; Anemia, Megaloblastic; Cells, Cultured; Fibroblasts; Genetic Complementation Test; Homocystinuria; Humans; Methionine; Mutation; Vitamin B 12; Vitamin B 12 Deficiency

When patients are examined for possible cobalamin deficiency, great stress is often placed on the presence or absence of macrocytosis and anemia and on how low the serum cobalamin level is. The present study, however, shows that only 45 (64%) of 70 consecutively diagnosed patients with pernicious anemia, the most common cause of cobalamin deficiency, had very low cobalamin levels (less than 74 pmol/L [or less than 100 ng/L]). Anemia was absent in 13 (19%) of the patients, and macrocytosis was absent in 23 (33%) of the patients; such absence was particularly common when cobalamin levels were only slightly or moderately low (74 to 184 pmol/L). Coexisting iron deficiency was responsible for the absence of macrocytosis in nine patients. Of the ten patients with neither anemia nor macrocytosis, neurological disturbance was prominent in six, including four whose only noticeable abnormality was cerebral. These observations indicate that macrocytosis and anemia, two classic features of pernicious anemia, may be overstressed in our diagnostic approach. All subnormal serum cobalamin results are best viewed as pathological until proved otherwise. Emphasis on only very low cobalamin levels risks delaying the diagnosis of pernicious anemia in a substantial proportion of cases, particularly in those without anemia or macrocytosis.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Erythrocyte Indices; Erythrocytes, Abnormal; Female; Hemoglobins; Humans; Male; Middle Aged; Vitamin B 12; Vitamin B 12 Deficiency

During a 5 year period, 28 adult patients with megaloblastic anaemia (MA) were treated in University Hospital. 71% of the patients were Indians. Symptoms of anaemia was the main presenting complaint in 18 (64%) of patients while in 2 patients peripheral neuropathy was the main problem. Pancytopenia was a common finding (present in 18 (64%) patients) while 6 (21%) patients had severe thrombocytopenia (less than 20 x 10(9)/L). The peripheral blood morphology provided important diagnostic clues i.e. macrocytes and/or hypersegmented neutrophils seen in most patients. Concurrent iron deficiency 'dampened' the megaloblastic picture. Though most patients suffered from MA of nutritional origin, 3 patients were diagnosed to have pernicious anaemia and 2 patients had myelodysplastic syndrome. Important practice points were detection of concurrent infection and hypokalemia which necessitated appropriate treatment. The controversy of blood transfusion in treatment of MA and the importance of reassessing patients after treatment were highlighted.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Bone Marrow; Folic Acid; Humans; Pancytopenia; Vitamin B 12

The results of an Interregional quality assurance scheme for tests in the diagnosis of megaloblastic anaemia were reviewed to assess the methods used. Serum folate assays showed great variation between methods, partly due to limitations in assessment by external quality assurance. Red cell folate assays yielded widely different results and much imprecision due both to the differences in preparation of the haemolysate and to the problems inherent in radioassay of a mixture of folate compounds. Intrinsic factor antibody tests showed appreciable variation in sensitivity. There was considerable inconsistency in the detection of polymorph nuclear hypersegmentation.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Antibodies; Erythrocytes; Folic Acid; Humans; Intrinsic Factor; Laboratories; Methods; Neutrophils; Quality Control; Vitamin B 12

The figures obtained in simultaneous radioimmunological assays of serum folate and vitamin B12 concentrations and erythrocyte folate concentration in 74 patients are presented. All these patients had a regular daily intake of over 80 g ethyl alcohol and presented an increase in mean blood cell volume. Most of the patients were males hospitalised with liver disease and/or anaemia. All were given bone narrow needle aspirations and liver biopsies. 46% of the patients presented a reduction in erythrocyte folates but vitamin B12 deficiency was rarely encountered. Megaloblastic transformation of the bone narrow was present in 56% of the alcoholics with reduced erythrocyte folates and in 10% of those with normal folate concentration. No correlation was found between serum and erythrocyte folate concentration and degree of liver damage. Serum vitamin B12 levels were higher in patients with cirrhosis. Inadequate diet was frequently found in the alcoholics with reduced folate concentrations. Due to variations in patient selection it is difficult to compare these data with those of other series but they do seem to confirm the hypothesis that the macrocytosis in most "healthy" alcoholics reflects a direct toxic action of the alcohol on erythropoiesis. In contrast folate deficiency is found among "derelict" chronic alcoholics in whom the vitamin deficiency has often not yet produced megaloblastosis of the bone marrow.

Topics: Adult; Aged; Aged, 80 and over; Alcoholism; Anemia, Macrocytic; Anemia, Megaloblastic; Erythrocytes; Female; Folic Acid; Humans; Male; Middle Aged; Vitamin B 12

A case of megaloblastic anaemia probably caused by malabsorption is analysed. Blood potassium levels were monitored before and during treatment with vitamin B12. It is concluded that low potassium levels in chronically hypoxic patients may be dangerous and that blood potassium should be monitored constantly during the treatment of this type of anaemia.

Topics: Aged; Aged, 80 and over; Anemia, Macrocytic; Anemia, Megaloblastic; Humans; Hypokalemia; Male; Vitamin B 12

A male infant with methyl-B12 deficiency (cblE) presented at age 6 weeks with lethargy, staring spells, and vomiting. He later became hypotonic and unresponsive to stimuli and required intubation and ventilation. He had homocystinuria and hypomethioninemia with megaloblastic anemia but normal serum folate and vitamin B12 concentrations. No methylmalonic aciduria was detected. Fibroblasts, cultured from the patient, were unable to grow in medium in which homocysteine replaced methionine and incorporated abnormally small amounts of [14C]-methyl-tetrahydrofolate but normal amounts of [14C]-propionate into protein. Methyl-B12 content of fibroblasts was low, while the adenosyl-B12 content was normal. Methionine synthase activity was decreased when the assay was performed under both optimal and suboptimal reducing conditions, suggesting heterogeneity in the cblE disease. The patient responded dramatically to hydroxocobalamin treatment. Homocystinuria disappeared after 10 days of therapy, and methionine was normalized after 3 weeks. Psychometric testing at age 15 months showed a developmental age of 9 months.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Cells, Cultured; Fibroblasts; Homocysteine; Homocystinuria; Humans; Infant; Male; Methionine; Vitamin B 12; Vitamin B 12 Deficiency

We present findings on an infant with neonatal megaloblastic anemia, homocystinuria, and neurologic dysfunction that included developmental delay and tonic seizures. There was no methylmalonic aciduria. Cyanocobalamin therapy was accompanied by complete hematologic and neurologic recovery, diminished homocystine excretion, and subsequently normal neurologic development. Cultured fibroblasts and lymphoblasts showed a reduced methionine synthase activity and a growth requirement for methionine. Cobalamin incorporation by the patient's lymphoblasts was normal, but the proportion of cellular methylcobalamin in the patient's lymphoblasts and fibroblasts were markedly reduced and that of adenosylcobalamin normal. The reduced methionine synthase activity was independent of assay reducing (thiol) conditions, but normal levels of activity accompanied culture of the patient's lymphoblasts in medium with markedly increased cobalamin concentration. The characteristics of the reduced methionine synthase of our patient differ significantly from that of the previously described infant with cobalamin E disease and suggest that genetic heterogeneity may characterize this mutation.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Anemia, Macrocytic; Anemia, Megaloblastic; Cell Division; Fibroblasts; Homocystinuria; Humans; Infant; Lymphocytes; Male; Methyltransferases; Vitamin B 12

Topics: Adolescent; Adult; Aged; Anemia, Megaloblastic; Biological Assay; China; Female; Folic Acid; Humans; Lactobacillus; Male; Middle Aged; Vitamin B 12

Topics: Anemia, Megaloblastic; Homocystinuria; Humans; Infant; Male; Metabolism, Inborn Errors; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adolescent; Anemia, Macrocytic; Anemia, Megaloblastic; Diphyllobothriasis; Feeding Behavior; Humans; Intestinal Diseases, Parasitic; Male; Niclosamide; Vitamin B 12

Five cases of severe megaloblastic anaemia in Gambians are described. Three of the patients were found to have pernicious anaemia. The difficulties in diagnosis and the various features of pernicious anaemia in Negroes are discussed. A brief review of the literature is included.

Topics: Adolescent; Adult; Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Erythrocyte Indices; Female; Folic Acid; Gambia; Hemoglobins; Humans; Male; Middle Aged; Vitamin B 12; Vitamin B 12 Deficiency

Megaloblastic anaemia in infancy is uncommon in western countries. We describe a case of an exclusively breast-fed monozygous twin with severe vitamin B12 deficiency with haematologic and neurologic abnormalities. Treatment with vitamin B12 resulted in a rapid haematological and clinical improvement.

Topics: Adult; Anemia, Macrocytic; Anemia, Megaloblastic; Breast Feeding; Diseases in Twins; Female; Humans; Infant; Iron Deficiencies; Male; Twins; Twins, Monozygotic; Vitamin B 12; Vitamin B 12 Deficiency

Megaloblastic anaemia due to bacterial overgrowth of the small intestine is due to vitamin B12 malabsorption. This report describes a patient with bacterial overgrowth of the small intestine who had megaloblastic anaemia and malabsorption of vitamin B12, but persistently normal levels of serum vitamin B12 and normal serum and red cell folate levels. However, there was evidence of vitamin B12 deficiency as shown by an abnormal deoxyuridine suppression test and by the response to treatment with physiological doses of vitamin B12. A relative increase in biologically inactive vitamin B12 analogues may be the explanation for the normal vitamin B12 level in this patient.

Topics: Aged; Anemia, Macrocytic; Anemia, Megaloblastic; Female; Humans; Intestine, Small; Vitamin B 12; Vitamin B 12 Deficiency

138 Indian patients with megaloblastic haemopoiesis were studied. All were lifelong vegetarians. The diagnosis was nutritional cobalamin deficiency in 95 and pernicious anaemia in 20; only 4 patients had folate deficiency. A third had intestinal malabsorption, 20 had features of osteomalacia, and 87 were iron deficient. Tuberculosis was diagnosed in 17. Cobalamin deficiency may have contributed to these complications via intestinal malabsorption and impaired bacterial killing of phagocytosed bacilli by cobalamin-deficient macrophages. The frequency of pernicious anaemia was the same in Indian subjects as in Caucasians.

Topics: Absorption; Adolescent; Adult; Aged; Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Antibodies; Child; Diet, Vegetarian; England; Erythrocytes; Female; Folic Acid; Humans; India; Intestinal Mucosa; Intestines; Iron Deficiencies; Male; Middle Aged; Religion; Vitamin B 12; Vitamin B 12 Deficiency

Three siblings presented in their second year of life with megaloblastic anemia that responded to parenteral cobalamin (Cbl). Schilling tests were less than 1%, correcting to 5 to 15% after addition of hog intrinsic factor (IF). Gastric acid analysis and gastric biopsies were normal by light and electron microscopy. Gastric juice contained less than 3 pmol/ml of Cbl-binding ability due to IF (normal, 10-34 pmol/ml) and less than 2 pmol/ml of IF when measured with a radioimmunoassay (RIA) using normal human IF-[57Co]Cbl and rabbit anti-human IF serum (normal, 17-66 pmol/ml). However, RIA employing rabbit anti-hog IF serum gave values of 4-13 pmol/ml of IF (normal, 11-33 pmol/ml). This material had an apparent molecular weight of 40,000 (normal IF = 70,000). The IF from gastric biopsies appeared normal in terms of Cbl-binding ability, ileal binding, molecular weight, and both RIAs. This IF differed from normal mucosal IF, in that it lost its Cbl-binding ability when incubated at 37 degrees C at acid pH or in the presence of pepsin or trypsin. This loss was retarded when [57Co]Cbl was bound to the IF before these incubations. The stabilizing effects of neutralization and Cbl were also demonstrated in vivo. Schilling tests for the siblings of 0.4, 0.5, and 1.0% increased to 2.7, 5.7, and 4.3% (P less than 0.05), respectively, when the Schilling tests were repeated with the addition of NaHCO3 and cobinamide (which allows Cbl to bind immediately to IF). We conclude that Cbl malabsorption in these children is due to an abnormal IF that is markedly susceptible to acid and proteolytic enzymes which cause a decrease in its molecular weight and Cbl-binding ability and a loss of antigenic determinants that are recognized by the anti-human IF serum.

Topics: Anemia, Megaloblastic; Child; Child, Preschool; Gastric Juice; Gastric Mucosa; Humans; Hydrogen-Ion Concentration; Intestinal Absorption; Intrinsic Factor; Molecular Weight; Peptide Hydrolases; Vitamin B 12

A Syrian family is described with three children who had inherited selective vitamin B12 malabsorption associated with proteinuria. (Imerslund-Grasbeck syndrome). Although inherited the defect was apparently not present at birth. A third child had less severe vitamin B12 malabsorption, was not vitamin B12 deficient and had no proteinuria. Studies on two of the affected children with subcellular fractionation of the uptake of radioactive vitamin B12 by ileal tissue in vivo indicate a defect in the ileal receptors for IF-bound vitamin B12. These findings are different from the single in vitro experiment on a patient with this condition that has been previously reported.

Topics: Adolescent; Adult; Anemia, Megaloblastic; Child; Child, Preschool; Humans; Ileum; Infant; Malabsorption Syndromes; Male; Proteinuria; Subcellular Fractions; Syndrome; Vitamin B 12

For 154 subjects, we verified that vitamin B12 and folate status was normal, using as criteria the average polymorphonuclear lobe count, mean corpuscular volume, and hemoglobin concentration. We then used blood from these subjects to compare values obtained with two radioassay kits, each designed for simultaneous vitamin B12 and folate determination. Although regression analysis showed reasonable correlation between the folate (r = 0.87) and vitamin B12 (r = 0.94) kits, we observed significant differences in the overall mean values for vitamin B12 (p less than 0.01) and folate (p less than 0.001) as measured with the kits in this population. Radioassay standard-curve data for the folate assays were similar, but these data indicated greater sensitivity at low concentrations for one vitamin B12 kit than the other. Using reference intervals recommended in the kit inserts, we found that the vitamin B12 status for 9% of these subjects would have been misclassified by one kit, 2% by the other.

Topics: Anemia, Megaloblastic; Erythrocyte Indices; Female; Folic Acid; Hemoglobins; Humans; Leukocyte Count; Male; Radioimmunoassay; Reagent Kits, Diagnostic; Reference Values; Sex Factors; Vitamin B 12

The first case of megaloblastic anemia due to selective malabsorption of vitamin B(12) and vitamin B(12)-intrinsic factor is described in an otherwise normal female adult, in whom pernicious anemia had previously been diagnosed.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Female; Humans; Ileum; Intrinsic Factor; Vitamin B 12

The activity of the two folate dependent enzymes supplying carbon 2 and carbon 8 of the purine nucleus was assayed in the bone marrow of rats and man, as well as in rat livers. The activity of both enzymes was several fold greater in marrow than in liver. Inactivation of cobalamin by exposure to nitrous oxide did not affect the enzymes in rat marrow cells, although an appreciable effect on hepatic enzymes was found. The depression of hepatic glycinamide ribotide (GAR) transformylase in rats exposed to nitrous oxide was prevented by supplying a formate precursor, methylthioadenosine. There was a considerable rise in the activity of GAR transformylase in human marrow cells from patients with megaloblastic anaemia due to cobalamin deficiency but no change in activity in marrow from patients deficient in folate.

Topics: Acyltransferases; Adenosine; Anemia, Megaloblastic; Animals; Bone Marrow; Deoxyadenosines; Humans; Hydroxymethyl and Formyl Transferases; Liver; Male; Methionine; Nitrous Oxide; Phosphoribosylaminoimidazolecarboxamide Formyltransferase; Phosphoribosylglycinamide Formyltransferase; Purines; Rats; Rats, Inbred Strains; Thionucleosides; Vitamin B 12; Vitamin B 12 Deficiency

Two elderly patients with vitamin B12 deficiency were found to have low immunoglobulin levels. These returned to normal on treatment with vitamin B12.

Topics: Aged; Anemia, Macrocytic; Anemia, Megaloblastic; Female; Humans; Immunoglobulins; Male; Vitamin B 12

S-adenosylmethionine (SAM) has antidepressant properties. The commonest neuropsychiatric complication of severe folate deficiency is depression. These independent observations suggest that methylation in the nervous system may underlie the expression of mood and related processes and may be implicated in some affective disorders; suggest new biological approaches to the understanding and treatment of some affective disorders; and may explain why methionine sometimes aggravates schizophrenia.

Topics: Anemia, Megaloblastic; Brain; Depressive Disorder; Emotions; Folic Acid Deficiency; Humans; Methylation; S-Adenosylmethionine; Schizophrenia; Vitamin B 12; Vitamin B 12 Deficiency

Cultured fibroblasts from a recently described patient with homocystinuria and megaloblastic anemia of infancy without methylmalonic aciduria were previously shown to have normal cobalamin uptake and a specific decrease in the proportion of intracellular methylcobalamin. As in control cells but unlike in those from patients with combined homocystinuria and methylmalonic aciduria (cobalamin C and cobalamin D), accumulated 57Co-labeled cobalamin was bound in appropriate amounts and proportion to intracellular binders which are known to be the two vitamin B12-dependent enzymes, methionine synthetase and methylmalonyl-CoA mutase. Despite the association of a normal quantity of intracellular cobalamin with methionine synthetase, the proportion of intracellular cobalamin which was methyl-B12 was below normal and in the range observed in cobalamin C and D cells. This methyl-B12 was decreased by exposure of fibroblasts in culture to nitrous oxide as was observed with control cells. Exposure of control fibroblasts during culture, but not of fibroblasts from this patient, to nitrous oxide significantly reduced the holoenzyme activity of methionine synthetase assayed in cell extracts. In addition, although methionine synthetase activity in cell extracts of control and cells from the patient were similar in the presence of standard assay concentrations of thiols, at low thiol concentrations, methionine synthetase activity in extracts of cells from the patient was much lower than in control extracts. Mixing of control patient extracts corrected this decreased activity in excess of that explained by addition of the individual activities added. The defect of this patient appears to be in a reducing system required for methionine synthesis.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Anemia, Macrocytic; Anemia, Megaloblastic; Cells, Cultured; Fibroblasts; Homocystinuria; Humans; Methionine; Nitrous Oxide; Vitamin B 12

Topics: Adolescent; Anemia, Macrocytic; Anemia, Megaloblastic; Humans; Male; Vitamin B 12

In DNA synthesis deoxythymidine kinase (TK) catalyses the conversion of deoxythymidine to deoxythymidine monophosphate (dTMP) via the 'salvage pathway'. Serum deoxythymidine kinase (S-TK) was measured in this study in 75 patients with vitamin B12 deficiency by a new, very sensitive method, using 125I-deoxyuridine as substrate. Elevated S-TK levels were found in those patients who had developed haemolysis and anaemia and the more advanced the disease the higher the S-TK value. Thus there was a highly significant correlation between S-TK, haemoglobin level and lactic dehydrogenase activity. These findings are consistent with the theory that elevated levels of S-TK are due to release from unstable proliferating tissue.

Topics: Anemia, Hypochromic; Anemia, Megaloblastic; Hemoglobins; Humans; L-Lactate Dehydrogenase; Thymidine Kinase; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Diagnosis, Differential; FIGLU Test; Folic Acid; Humans; Vitamin B 12

We describe an inborn error of vitamin B12 metabolism in an infant who had severe developmental delay, megaloblastic anemia, and homocystinuria. There was no evidence of methylmalonic aciduria or deficiency of folate or vitamin B12. Treatment with hydroxocobalamin, but not with cyanocobalamin and folic acid, resulted in rapid clinical and biochemical improvement. Cultured fibroblasts showed an absolute growth requirement for methionine, defective incorporation of radioactivity from [14C]5-methyltetrahydrofolate into protein, and normal incorporation of radioactivity from [14C]propionate, thus assigning the intracellular defect to methionine synthesis. The proportion of intracellular methylcobalamin in the fibroblasts was decreased, but that of 5'-deoxyadenosylcobalamin was normal. Methionine synthetase activity in cell extracts was normal, as was cobalamin incorporation into cultured cells. This defect differs from those described previously in being limited to methylcobalamin accumulation and defective use of 5-methyltetrahydrofolate by intact cells with normal activity of methylmalonyl CoA mutase.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Amino Acid Metabolism, Inborn Errors; Anemia, Macrocytic; Anemia, Megaloblastic; Cobamides; Fibroblasts; Homocystinuria; Humans; Hydroxocobalamin; Infant, Newborn; Male; Methionine; Propionates; Tetrahydrofolates; Vitamin B 12

Topics: Adolescent; Adult; Anemia, Hypochromic; Anemia, Megaloblastic; Female; Folic Acid; Folic Acid Deficiency; Humans; Male; Middle Aged; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Megaloblastic; Child, Preschool; Female; Humans; Malabsorption Syndromes; Proteinuria; Vitamin B 12

A new solid phase vitamin B12 assay is described using intrinsic factor to measure microbiologically-available B12 and R-binder to measure total B12. The solid phase reagent consists of intrinsic factor coupled to polyacrylamide beads and salivary R-binder coupled to polyacrylamide beads. The assay is simple to perform and separates completely sera from controls and patients with megaloblastic anaemia due to B12 deficiency.

Topics: Acrylic Resins; Anemia, Megaloblastic; Humans; Hydrogen-Ion Concentration; Intrinsic Factor; Light; Methods; Nuclear Proteins; Nucleoproteins; Osmolar Concentration; Time Factors; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Autoantibodies; Deoxyuridine; Erythrocyte Indices; Folic Acid; Humans; Intrinsic Factor; Reagent Kits, Diagnostic; Schilling Test; Vitamin B 12

Topics: Aged; Anemia, Macrocytic; Anemia, Megaloblastic; Diabetes Mellitus; Female; Humans; Malabsorption Syndromes; Metformin; Vitamin B 12; Vitamin B 12 Deficiency

One or more episodes of recurrent megaloblastic anemia occurred in 36 (10.8 percent) of 333 patients with pernicious anemia following interruption of therapy. Treatment had most commonly been discontinued by patients because they felt well, or by physicians due to error. Thirty-five episodes of recurrent cobalamin deficiency were analyzed in detail. In the 24 patients in whom the exact date of cessation of therapy was recorded, the mean interval before relapse was diagnosed was 64.5 months (range 21 to 123 months). Recurrence manifested as macrocytosis in the absence of anemia occurred earlier (mean, 49.2 months) than that associated with anemia (73.1 months). A weak correlation was apparent between the amount of previous cyanocobalamin treatment and time to relapse. One third of relapses were unrecognized and left untreated for more than two years, while usually slow hematologic progression occurred. Recurrences of cobalamin deficiency in individual patients exhibited mimetic features. Further study is necessary to establish the optimal dosage and frequency of maintenance therapy in pernicious anemia.

Topics: Adult; Aged; Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Fatigue; Female; Glossitis; Hematocrit; Humans; Male; Medication Errors; Middle Aged; Recurrence; Time Factors; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Humans; Infant; Vitamin B 12; Vitamin B 12 Deficiency

The incidence and pathogenesis of acute megaloblastic bone-marrow change and of abnormalities in DNA synthesis, as assessed with the deoxyuridine(dU) suppression test, have been investigated in a prospective study of 70 seriously ill patients admitted to an intensive-care unit. On admission megaloblastic bone-marrow change was present in 22 patients, 18 of whom had been anaesthetised with nitrous oxide for 2-6 h during surgical procedures before admission. 16 of these 18 patients died, compared with 7 of 22 patients in whom haemopoiesis remained normoblastic despite receiving equivalent amounts of nitrous oxide. An abnormal dU-suppression test developed only in patients who had received nitrous oxide; on admission an abnormal dU-suppression test was found in 39 of the 42 patients tested who had been exposed to the anaesthetic. The abnormality produced in the dU-suppression test by nitrous oxide in patients admitted to the intensive-care unit was more severe and recovery was slower than the abnormality seen in patients undergoing cardiac-bypass surgery. During the recovery period from the effects of nitrous oxide the pattern of correction of the dU-suppression test changed from that of vitamin-B12 deficiency to folate deficiency.

Topics: Adolescent; Adult; Aged; Anemia, Macrocytic; Anemia, Megaloblastic; Anesthesia; Bone Marrow; Child; Deoxyuridine; DNA; Female; Folic Acid; Folic Acid Deficiency; Hematopoiesis; Humans; Intensive Care Units; Male; Middle Aged; Nitrous Oxide; Vitamin B 12

Topics: Anemia, Megaloblastic; Bone Marrow; Hematopoiesis; Humans; Nitrous Oxide; Vitamin B 12

The role of vitamin B12 in the folate dependent biosynthesis of thymidine nucleotides is controversial. In an attempt to clarify this, three methods have been used to assess the relative efficacy of vitamin B12 (hydroxocobalamin) and various folate analogues in titrated concentrations at correcting 'de novo' thymidylate synthesis by megaloblastic human marrow cells: (1) The deoxyuridine (dU) suppression test which analyses the reduction in (3H)-thymidine labeling of DNA by unlabeled dU. Marrow cells were also labeled with (6-3H)-dU with assessment of (2) its incorporation into DNA and (3) the accumulation of (6-3H)-deoxyuridine monophosphate (3H-dUMP). The three methods gave similar results. In both, N6-formyl tetrahydrofolate (formyl-FH4) was the most effective agent at correcting thymidylate synthesis in megaloblastic anemia due to vitamin B12 or folate deficiency. Vitamin B12 corrected the lesion in vitamin B12 deficiency but not in folate deficiency. Tetrahydrofolate (FH4) and folic acid were effective in deficiency of vitamin B12 or folate, although in both deficiencies they were less effective than formyl-FH4. Methyl-FH4 was effective in folate deficiency but not in vitamin B12 deficiency. These results confirm the failure of methyl-FH4 utilisation in vitamin B12 deficiency. They suggest that if vitamin B12 is needed in the formylation of FH4, this is a minor role in provision of the correct coenzyme for thymidylate synthesis compared with its major role of provision of FH4 from methyl-FH4.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Bone Marrow; Deoxyuridine; DNA; Folic Acid; Folic Acid Deficiency; Humans; Leucovorin; Tetrahydrofolates; Thymine Nucleotides; Vitamin B 12; Vitamin B 12 Deficiency

The activities of 5-methyltetrahydrofolate (5-CH3THF) related enzymes and DNA polymerase alpha were determined in bone marrow cells obtained from patients with vitamin B12 deficient megaloblastic anemia and compared with those from healthy volunteers and patients with hemolytic anemia. 5-CH3THF homocysteine methyltransferase activity was significantly lower than that in the control subjects. 5,10-methylenetetrahydrofolate reductase activity was only slightly elevated to that in the control subjects. DNA polymerase alpha activity was significantly higher than that in the control. High deoxyuridine suppression test values in vitamin B12 deficient bone marrow cells were improved by tetrahydrofolate, but not by 5-CH3THF. These data indicate that, even though the reverse reaction catalyzed by 5,10-methylenetetrahydrofolate reductase may be operative in vitamin B12 deficiency, it is not sufficient to correct the disturbance in folate metabolism in vitamin B12 deficiency. Increased DNA polymerase alpha activity may be due to compensation for disarranged DNA synthesis.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; 5,10-Methylenetetrahydrofolate Reductase (FADH2); Adult; Aged; Alcohol Oxidoreductases; Anemia, Macrocytic; Anemia, Megaloblastic; Bone Marrow; Bone Marrow Cells; Deoxyuridine; DNA Polymerase II; DNA-Directed DNA Polymerase; Female; Folic Acid; Humans; Hydroxocobalamin; Leucovorin; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Tetrahydrofolates; Thymidine; Vitamin B 12; Vitamin B 12 Deficiency

We studied two brothers (J.R. and M.R.) with the cobalamin D variant of congenital methylmalonic aciduria-homocystinuria, whose previously reported lack of megaloblastic anemia conflicted with current concepts of cobalamin's role in DNA synthesis and the "methyltetrahydrofolate (MTHF) trap" hypothesis. Both subjects were indeed hematologically normal, although J.R. had a mean corpuscular volume of 96 fl. However, both demonstrated abnormalities in the deoxyuridine suppression test. J.R. had an abnormal suppression value of 21.0% (normal less than 10%) that was correctable by adding hydroxocobalamin or folic acid in vitro but not MTHF. M.R. had normal suppression (8.9%), but demonstrated worsening (18.6%) when MTHF was added. J.R.'s classical deoxyuridine suppression pattern of cobalamin deficiency thus supports the trap hypothesis. However, his lack of comparable morphological changes suggests that impaired de novo thymidylate synthesis and the trap hypothesis, though valid, may not fully account for the megaloblastic maturation accompanying cobalamin deficiency. Equally noteworthy was the deleterious effect of MTHF on M.R.'s marrow, suggesting its potential usefulness as an in vitro "stress test" for latent cobalamin abnormality.

Topics: Adolescent; Adult; Anemia, Megaloblastic; Bone Marrow; Deoxyuridine; Homocystinuria; Humans; Male; Metabolism, Inborn Errors; Methylmalonic Acid; Tetrahydrofolates; Thymidine; Vitamin B 12

Topics: Adolescent; Anemia, Macrocytic; Anemia, Megaloblastic; Child; Humans; Malabsorption Syndromes; Metabolism, Inborn Errors; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin E Deficiency

Topics: Aged; Anemia, Macrocytic; Anemia, Megaloblastic; Diagnosis, Differential; Humans; Male; Megaloblasts; Vitamin B 12

Topics: Adult; Anemia, Macrocytic; Anemia, Megaloblastic; Female; Folic Acid; Hematopoietic Stem Cells; Humans; Liver Cirrhosis; Male; Thymidine; Vitamin B 12

Topics: Adult; Aged; Anemia, Macrocytic; Anemia, Megaloblastic; Bone Marrow; Erythropoiesis; Female; Folic Acid; Humans; Male; Middle Aged; Peritoneal Dialysis; Renal Dialysis; Vitamin B 12

Owing to the higher serum cobalamin results that are obtained by R-binder radioisotopic dilution assay compared to microbiological assays (E. gracilis and L. leichmannii) it was suggested that serum contained a cobamide(s) that could not be detected by the more specific microbiological assays and that a much less specific test organism, which responds to most naturally occurring cobamides, such as the cobamide-dependent E. coli mutant, might respond to these cobamide(s) in serum. In an attempt to investigate this possibility an improved and simplified E. coli assay for the measurement of cobamide in serum was developed. The method is described, and the results obtained in normal subjects, in patients with megaloblastic anemia, and in anaemic pregnant women not suffering from megaloblastic anaemia are reported and compared with E. gracilis assay results.

Topics: Anemia, Hypochromic; Anemia, Megaloblastic; Anemia, Pernicious; Biological Assay; Cobamides; Escherichia coli; Euglena gracilis; Female; Humans; Pregnancy; Pregnancy Complications, Hematologic; Vitamin B 12

Topics: Adult; Anemia, Macrocytic; Anemia, Megaloblastic; Humans; Leukemia, Myeloid, Acute; Male; Vitamin B 12

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Biological Assay; Diagnostic Errors; Humans; Radioisotope Dilution Technique; Vitamin B 12

A patient with sickle cell trait and pernicious anemia in relapse may appear to have sickle thalassemia because HbA2 levels can be elevated and the peripheral blood smear may contain target cells, teardrop cells, and eliptocytes. A normal hemoglobin alpha:beta chain ratio, a megaloblastic bone marrow, and correction of the abnormal hematologic morphology after administration of vitamin B12 will establish the correct diagnosis.

Topics: Adult; Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Diagnosis, Differential; Female; Humans; Sickle Cell Trait; Thalassemia; Vitamin B 12

A ligand assay specific for cobalamin that uses mouse stomach as the source of intrinsic factor has been developed. When mouse stomach extract incubated with radiocobalamin is fractionated by gel chromatography, the radioactive complex elutes as a single peak with apparent molecular weight of 54,900. Formation of the complex is greater than 98% inhibited by human anti-intrinsic factor antibody. When the equivalent of 10,000 pg/ml of cobinamide is added to serum, the apparent cobalamin concentration detected averages 8.5 pg/ml. Correlation with the Lactobacillus leichmannii microbiologic assay results in the regression equation y = 0.97x + 20. In six patients who had megaloblastic anemia the serum cobalamin by the mouse intrinsic factor ligand assay ranged from 0 to 9 pg/ml. Because the primary source of intrinsic factor is free of R proteins, there is no need for extensive purification of the extract. The assay is sensitive, precise, and accurate, and no more difficult to perform than other conventional ligand assay procedures.

Topics: Anemia, Megaloblastic; Animals; Antibodies; Chromatography, Gel; Humans; Intrinsic Factor; Lactobacillus; Mice; Protein Binding; Radioligand Assay; Saliva; Stomach; Vitamin B 12

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Child, Preschool; Female; Humans; Infant; Malabsorption Syndromes; Male; Proteinuria; Vitamin B 12

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Folic Acid; Humans; L-Lactate Dehydrogenase; Vitamin B 12

A young Australian woman developed a severe nutritional megaloblastic anaemia due to poor intake of vitamin B12 and, possibly, of folic acid. Simple dietary advice resulted in an adequate intake of vitamin B12 and folic acid, and in maintenance of normal serum levels of both vitamins.

Topics: Adult; Anemia, Macrocytic; Anemia, Megaloblastic; Female; Folic Acid; Folic Acid Deficiency; Humans; Vitamin B 12; Vitamin B 12 Deficiency

The minimal daily requirement of dietary vitamin B12 is defined as that amount which must be ingested in the diet to prevent the occurrence of megaloblastosis, anemia, or other manifestations of vitamin B12 deficiency. An attempt has been made to define this requirement by studying hematological responses to varying amounts of the vitamin in five south Indian subjects with vitamin B12 deficiency anemia (one due to gastric atrophy and four due to dietary deficiency). Amounts ranging from 0.07 to 0.25 micrograms of dietary vitamin B12 were shown to be inadequate but amounts ranging from 0.3 to 0.65 microgram were adequate or possibly more than adequate. It is concluded that the minimal daily requirement of dietary vitamin B12 for the average south Indian adult is in the region of 0.5 microgram/day and that an intake of 1.0 microgram/day would cover the needs of the vast majority of the population and allow a wide margin of safety.

Topics: Adult; Anemia, Megaloblastic; Bone Marrow Cells; Diet; Dose-Response Relationship, Drug; Female; Hemoglobinometry; Humans; Male; Middle Aged; Nutritional Physiological Phenomena; Nutritional Requirements; Reticulocytes; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Alcoholism; Anemia, Macrocytic; Anemia, Megaloblastic; Bone Marrow; Folic Acid; Humans; Liver; Male; Middle Aged; Vitamin B 12

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Child; Child, Preschool; Female; Humans; Infant; Malabsorption Syndromes; Proteinuria; Syndrome; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Megaloblastic; Animals; Bone Marrow; Deoxyuridine; Folic Acid; Humans; Male; Rats; Rats, Inbred Strains; Thymidine; Vitamin B 12

Topics: Aged; Aminosalicylic Acid; Anemia, Macrocytic; Anemia, Megaloblastic; Anticonvulsants; Antineoplastic Agents; Colchicine; Humans; Hydroxocobalamin; Intestinal Absorption; Neomycin; Stomach Neoplasms; Vitamin B 12; Vitamin B 12 Deficiency

Quality control trials have shown that, in routine practice, serum vitamin B12 estimations vary so much from laboratory to laboratory that serious confusion can result irrespective of whether microbiological or radioassay methods are used. Even experienced centres find the assay too insensitive and non-specific for a low level to be used as the sole criterion of vitamin B12 deficiency; the haemopoietic and biochemical sequelae of vitamin B12 deficiency also correlate poorly with the serum level. These basic difficulties with the assay seem to stem from the pattern of vitamin B12 (or cobalamin) binding in serum. Human beings are unique in having virtually all of their cobalamin attached to an apparently functionless binder, transcobalamin I. It is therefore not surprising that the serum cobalamin is such a poor predictor of cobalamin deficiency. The metabolically important serum binder is transcobalamin II and deficiency of this protein causes a potentially lethal megaloblastic anaemia even though the serum cobalamin level is normal. Tissue cobalamin depletion with normal serum levels also occurs after nitrous oxide inhalation and in certain inborn errors of metabolism.

Topics: Anemia, Megaloblastic; Biological Assay; Humans; Quality Control; Reference Values; Schilling Test; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

The facts known today about the occurrence and possible mechanisms of anaemias caused by medicaments are represented in a survey. In this connection toxic haemolytic anaemias, immunohaemolytic anaemias, toxic aplastic anaemias, megaloblastic anaemias, and some other, more rarely occurring types are referred to.

Topics: Alcoholism; Anemia; Anemia, Aplastic; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune; Anemia, Megaloblastic; Anemia, Sideroblastic; Antitubercular Agents; Benzenesulfonates; Bone Marrow; Chloramphenicol; Chromosome Aberrations; Contraceptives, Oral, Hormonal; Folic Acid Antagonists; Gastrointestinal Hemorrhage; Humans; Preleukemia; Purines; Pyrimidines; Vitamin B 12

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Diabetes Mellitus; Female; Humans; Intestinal Absorption; Metformin; Middle Aged; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Erythrocytes; Folic Acid; Humans; Vitamin B 12

The numerical behaviour of the leucocytes, thrombocytes and reticulocytes of 12 patients with megaloblastic anaemia before and after additional transfusion as well as after following parenteral therapy with vitamin B12 was investigated. Transfusions alone had no influence on the numbers of leukocytes thrombocytes and reticulocytes. After 4--5 days vitamin B12 led to a very inhibited crisis of reticulocytes in 9 of the 12 patients, in the others an increase did not take place. Thrombocytes and leukocytes appeared partly in form of a crisis in all patients after 6 to 9 days with normalisation of the values, latest after 14 days. The very reduced or lacking crisis of reticulocytes after treatment with vitamin B12 due to previous additional transfusion was discussed.

Topics: Aged; Anemia, Macrocytic; Anemia, Megaloblastic; Blood Transfusion; Erythrocyte Count; Humans; Middle Aged; Reticulocytes; Vitamin B 12

The study of vitamin B12 release from the ileal enterocyte has been hampered by the fact that B12 does not cross the serosa of traditional everted ileal sacs. We studied this release by perfusing the superior mesenteric arteries of starved, heparinized, etherized rats and collecting perfusate from the superior mesenteric vein. The rats were fed 57CoB12 well before study. The standard perfusion medium was Krebs-Henseleit-NaHCO3 buffer containing glucose, dextran, albumin, propranolol, and dexamethasone. The preparation utilized glucose and O2, produced lactate, and was relatively impermeable to [14C]inulin, to D-xylose, and to 57CoB12 bound to an inert human IF. Glucose placed in the gut lumen was transported much more rapidly than D-xylose. Vitamin B12 emerged in the perfusate bound to a protein with a molecular size similar to that of TC II. IF could not be identified in the perfusate. Rat serum, independently of its unsaturated TC II content, increased the rate of transfer of B12 into the perfusate.

Topics: Anemia, Megaloblastic; Animals; Binding Sites; Cattle; Erythrocytes; Hydrogen-Ion Concentration; Intestinal Absorption; Intestinal Mucosa; Male; Perfusion; Rats; Serum Albumin, Bovine; Time Factors; Vitamin B 12

Topics: Adult; Aged; Anemia, Macrocytic; Anemia, Megaloblastic; Erythrocyte Count; Erythrocyte Volume; Female; Folic Acid; Folic Acid Deficiency; Humans; Male; Middle Aged; Reticulocytes; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Megaloblastic; Cobalt Radioisotopes; Humans; Intestinal Absorption; Male; Sprue, Tropical; Vitamin B 12; Whole-Body Counting

The definitive diagnosis of pernicious anaemia (PA) in the elderly is by no means always straightforward, particularly when inappropriate medication has been introduced before the institution of specific investigatory procedures. A detailed haematological study was carried out on 301 patients aged 60-95 with a serum B(12) concentration at the laboratory's lower level of normal of 150 ng per litre (Euglena gracilis assay). The diagnosis of PA was based on strict predetermined haematological criteria. All patients were subsequently studied by the simultaneous oral administration of the dual isotopes (57)Co-labelled B(12) bound to intrinsic factor and free (58)Co-labelled B(12) (Dicopac test), and urine was collected over 24 hours after an intramuscular dose of 1 mg nonradioactive B(12) for estimation of the (57)Co/(58)Co B(12) ratio; 255 patients satisfied all criteria for final analysis. The Radiochemical Centre, Amersham suggests an upper limit of the normal range for the (57)Co/(58)Co ratio of 1.3 with a lower limit for PA of 2.0. We were unable to show a sharp borderline in the (57)Co/(58)Co B(12) ratio between those patients shown by other criteria to have PA and those who do not have PA; 34% of the 71 established patients had a ratio below 2.0. From our series a ratio borderline drawn at 1.4 gave only one false negative (1.4% of the PA group). Of the 175 non-PA cases, nine (5%) gave false positive results; four of these had (58)Co excretion levels high enough to make misdiagnosis unlikely. In a proportion of patients the (57)Co/(58)Co B(12) ratio was estimated at regular intervals for 36-hour periods. Maximum accuracy of isotope measurement on a single specimen was obtained 8-20 hours after isotope dosing. The Dicopac investigation is a useful simple screening test in the differential diagnosis of patients with a megaloblastic bone marrow and combined low serum B(12) and folate concentrations. When carried out by the standard technique, the degree of discrimination between normal and abnormal ratios is of limited diagnostic significance in one-third of patients.

Topics: Aged; Anemia, Megaloblastic; Anemia, Pernicious; Cobalt Radioisotopes; Diagnosis, Differential; Humans; Intrinsic Factor; Middle Aged; Vitamin B 12

We studied the rate of disappearance of neutrophil hypersegmentation in 23 patients with megaloblastic anemia during therapy with vitamin B12 and folic acid. In 14 patients with uncomplicated megaloblastic anemia, the neutrophil lobe average began to fall towards normal 11.4 +/- 0.3 (SEM) days after treatment was begun and became normal by 13.9 +/- 0.6 days. In nine patients with associated inflammatory disorders, the lobe average returned to normal more rapidly. In six initially neutropenic patients, a five-fold increase in total granulocyte count occurred by the eighth day and a seven-fold increment in the total number of circulating hypersegmented neutrophils. Granulocyte folate concentrations in five folate-deficient patients rose to normal levels within 4 to 7 days of starting therapy. Hypersegmentation thus persists for many days after correction of neutropenia and restoration of normal granulocyte folate levels have occurred. We conclude that cobalamin and folate are needed at two different steps in granulopoiesis.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Blood Cell Count; Folic Acid; Granulocytes; Humans; Neutrophils; Prospective Studies; Reticulocytes; Vitamin B 12

Renal biopsy material obtained from a 6 year old girl suffering from an Imerslund-Najman-Gräsbeck-syndrome was examined by light- and electron-microscopy. Clinically the patient presented the characteristic intrinsic factor independent vitamin B12 malabsorption with severe megaloblastic anemia and a benign nephropathy with non-selective proteinuria. Electron microscopic examination of the prenal glomeruli showed no obvious alterations of the Electron microscopic examination of the renal glomeruli showed no obvious alterations of the capillary basement membranes but revealed a considerable diffuse dilatation of the rough endoplasmic reticulum in the podocytes with accumulation of a finely fibrillar material within the widened cisternae. This finding is interpreted as an indication that the synthesis and/or secretory activities of the podocytes, as far as the basement membrane is concerned, and thus the basement membranes themselves, may be altered with the consequence of an increased permeability of the filtration barrier. Because proteinurie contrary to anemia did not respond to parenteral vitamin B12 therapy and therefore is obviously not vitamin B12 dependent, it is assumed that both vitamin B12 malabsorption and glomerulopathy in this hereditary disease are established by a pleiotropic gene or two closely associated genes.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Child; Female; Humans; Kidney Glomerulus; Malabsorption Syndromes; Microscopy, Electron; Proteinuria; Syndrome; Vitamin B 12

Thirteen patients with significant hemorrhage, severe thrombocytopenia, and megaloblastic bone marrows are described. Unusual features of this problem included its acute onset, frequent absence of the typical peripheral blood changes of megaloblastic anemia, normal serum B12 levels, and serum folates which were often not clearly abnormal. Most patients were critically ill and common clinical features included reduced dietary intake, renal failure, renal dialysis, the postoperative state, and sepsis. These clinical features, the laboratory findings, and a platelet increase in most patients after folate therapy lead to the conclusion that this problem is probably due to acute folic acid deficiency. Possible explanations for the atypical laboratory findings include the acuteness of onset, recent blood transfusion therapy, and impaired folate utilization. This problem may be relatively common. Because of its potential clinical importance, rapid onset, and attendent diagnostic difficulties, prophylactic folic acid is recommended in the clinical setting described.

Topics: Acute Disease; Anemia, Megaloblastic; Bone Marrow Examination; Folic Acid; Folic Acid Deficiency; Hemorrhage; Humans; Thrombocytopenia; Vitamin B 12

Despite the clinical use of the 'deoxyuridine suppression test' to document vitamin B12 or folate deficiency its biochemical basis is unclear and currently disputed. Because of this the metabolism of deoxyuridine in marrow cells has been examined. In normoblastic marrow cells the ratio of radio-labelled deoxyuridine to thymidine incorporation into DNA approximates one and preincubation of cells with unlabelled deoxyuridine results in progressive reduction of uptake of both radio-labelled deoxynucleosides. In the same cells methotrexate significantly reduces the DNA incorporation of deoxyuridine but not that of thymidine. In megaloblastic marrow the ratio of radio-labelled deoxyuridine to thymidine uptake is less than one and the reduced deoxyuridine uptake is not significantly altered by either cyanocobalamin or folic acid. With megaloblastic samples the reduction by deoxyuridine of radio-labelled deoxyuridine uptake is less marked than that observed with normoblastic cells and to achieve similar results requires folic acid. These findings suggest that reduced deoxyuridylate conversion to deoxythymidylate by thymidylate synthetase is appropriate to explain the 'deoxyuridine suppression test' in megaloblastic marrow cells and that altered substrate requirements for this activity may occur in megaloblastic cells.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Bone Marrow; Deoxyuridine; DNA; Folic Acid; Folic Acid Deficiency; Humans; Methotrexate; Thymidine; Thymidylate Synthase; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Megaloblastic; Humans; Vitamin B 12; Vitamin B 12 Deficiency

A 34-year-old Black woman had severe megaloblastic anemia in childhood. Initially, and over the years, she responded well to massive doses of parenteral cobalamin (Cbl) or oral folic acid. Metabolic reactions involving Cbl and folate enzymes were normal during both relapse and remission except for the absence of thymidylate synthetase in relapse. Amino acid analyses of urine and plasma showed no significant abnormalities. Neither cystathionine, homocystine, formiminoglutamic acid, nor methylmalonic acid was detected in the urine. The serum Cbl level was repeatedly elevated even when the patient was receiving only folic acid therapy. The elevation of the vitamin in the serum was found to be a result of markedly increased levels of transcobalamin II (TC II), as identified by several physicochemical techniques. The patient's TC II-Cbl shared immunologic properties with normal TC II but did not facilitate or impede the uptake of Cbl or Cbl bound to normal TC II, respectively, by human cells.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Blood Proteins; Female; Folic Acid; HeLa Cells; Humans; Hypergammaglobulinemia; Lymphocytes; Middle Aged; Protein Binding; Transcobalamins; Vitamin B 12

A case of the exclusively breast-fed infant of a vegetarian mother is reported. Neurological deterioration commenced between three and six months of age, and progressed to a comatose premoribund state by the age of nine months. Investigations revealed a mild nutritional vitamin B12 deficiency in the mother, and a very severe nutritional B12 deficiency in the infant, with severe megaloblastic anaemia. Treatment of the infant with vitamin B12 resulted in a rapid clinical and haematological improvement, but neurological recovery was incomplete. Evidence is presented that dietary B12 deficiency was the sole cause of the infant's deterioration, and the literature relating to the condition is reviewed. It is recommended that all strict vegetarians (vegans), especially women in the child-bearing age group, take vitamin B12 supplements.

Topics: Anemia, Megaloblastic; Brain Damage, Chronic; Diet, Vegetarian; Female; Humans; Infant; Male; Neurologic Manifestations; Vitamin B 12; Vitamin B 12 Deficiency

Charts of 122 patients with megaloblastic anemia due to either B12 or folic acid deficiency were reviewed for the presence of fever. Fever, defined as a temperature of 100 F (37.8 C) or more, was present in approximately 40% of the patients with both. The elevation was usually minimal but was sometimes over 104 F (40 C), usually in those with more severe anemia and thrombocytopenia, and greater elevations of SGOT and bilirubin concentration. In uncomplicated cases, the temperature returned rapidly to normal after adequate vitamin therapy. Failure of the fever to disappear rapidly with treatment should suggest the probability of some cause other than megaloblastic anemia.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Fever; Folic Acid; Folic Acid Deficiency; Humans; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Autoantibodies; Diagnosis, Differential; FIGLU Test; Gastric Juice; Gastritis; History, 18th Century; History, 19th Century; History, 20th Century; Humans; Intrinsic Factor; Prognosis; Vitamin B 12

We have studied a patient, unrelated to the patients previously described, with inherited lack of the vitamin B12 binding protein Transcobalamin II. Severe haematological abnormalities were found within a few weeks of birth and responded to treatment with both vitamin B12 and folic acid. He was maintained in partial remission with such treatment until adolescence, except for a time in early childhood when folic acid alone was given and he suffered severe neurological deterioration. A the age of 18 years he was admitted to hospital because of convulsions; the deoxyuridine suppression test showed intracellular deficiency of B12 despite a normal serum B12 and normal haemoglobin concentration. His serum failed to promote the uptake of radioactive B12 by bone marrow cells, and analysis of serum B12 binding proteins demonstrated the lack of Transcobalamin II. Treatment with injections of 1000 micrograms of B12 three times weekly corrected the abnormality shown in the deoxyuridine suppression test; following this treatment, together with changes in anticonvulsive therapy, he remains healthy without occurrence of further convulsions, and is haematologically normal.

Topics: Adult; Anemia, Macrocytic; Anemia, Megaloblastic; Blood Proteins; Bone Marrow; Deoxyuridine; Folic Acid; Humans; Intestinal Absorption; Male; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adult; Anemia, Macrocytic; Anemia, Megaloblastic; Humans; Intestinal Absorption; Male; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Child; Child, Preschool; Female; Humans; Infant; Male; Proteinuria; Syndrome; Vitamin B 12

Report on a case of severe megaloblastic anemia in a vegetarian, associated with marked erythroleukemic blood findings probably caused by infections (bronchopneumonia, asthmatic bronchitis, urinary tract infection) and severe heart failure. Successful treatment of the above mentioned complications resulted in almost complete disappearance of pathologic cells from the blood even before vitamin B12 treatment was started. With this therapy complete recovery was achieved and the signs suspect for erythroleukemia in blood and bone marrow disappeared definitively. The case also fulfilled all the criteria of pernicious anemia (Schilling's test and determination of intrinsic factor were not done).

Topics: Aged; Anemia, Macrocytic; Anemia, Megaloblastic; Bone Marrow Examination; Digitalis Glycosides; Diuretics; Female; Folic Acid; Heart Failure; Humans; Leukemia, Erythroblastic, Acute; Obesity; Vitamin B 12; Vitamin B 12 Deficiency

Deoxyuridine suppression of labelled thymidine uptake tests were performed in the bone marrows of 58 patients with megaloblastic anaemia (haemoglobin less than 10.0 g/dl) and invariably gave values (range 10.3-58.8%) above the range in 16 control marrows (range 1.0-9.0%). Folinic acid corrected the test equally well in either folate or vitamin B12 deficiency, even at concentrations as low as 60 ng/ml. Folic acid also corrected the test equally well in either deficiency but was only effective at concentrations down to 5 microgram/ml. Vitamin B12 (100 microgram/ml) only corrected the test in vitamin B12 deficiency and 5-methyltetrahydrofolate only corrected the test in folate deficiency at the concentrations tested between 60 and 1.2 microgram/ml. Among 16 patients with subnormal serum levels of both vitamin B12 and folate, vitamin B12 partially corrected the test in eight, including all five with pernicious anaemia, but had no effect in the other eight. Despite the clear-cut results of the dU suppression test, measurement of the deoxythymidine triphosphate (dTTP) concentration in normal and megaloblastic phytohaemagglutinin stimulated lymphocyte cultures or short-term bone marrow cultures gave no clear-cut differences between normal and megaloblastic cells after addition of deoxyuridine nor did the addition of vitamin B12, folic acid or folinic acid either alone or with deoxyuridine produce consistent changes in the dTTP concentration in lymphocytes or bone marrow cells in megaloblastic anaemia. Alcohol caused a rise in deoxyadenosine triphosphate concentration in normal PHA-stimulated lymphocytes which was concentration dependent but caused no consistent change in any of the other three deoxynucleoside triphosphate (dNTP) concentrations. Diphenylhydantoin (10(-3)M, 10(-4)M) had no consistent effect on any of the four dNTP concentrations.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Bone Marrow; Cells, Cultured; Deoxyadenine Nucleotides; Deoxyuridine; DNA; Ethanol; Folic Acid; Humans; Leucovorin; Lymphocytes; Tetrahydrofolates; Thymidine; Thymine Nucleotides; Vitamin B 12

The utilization of [14C]formate for serine synthesis by lymphocytes was impaired in all the patients with pernicious anaemia and in 70% of other patients with megaloblastic anaemia. In pernicious anaemia this was corrected by vitamin B12 therapy in 48 h but not by folate therapy although patients given folate showed a satisfactory haematological response.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Folic Acid; Folic Acid Deficiency; Formates; Humans; In Vitro Techniques; Lymphocytes; Serine; Vitamin B 12; Vitamin B 12 Deficiency

Serum ferritin concentrations have been estimated in 30 patients with untreated megaloblastic anaemia, 27 with Addisonian pernicious anaemia. A significant difference was found between the mean serum ferritin level of the 27 pernicious anaemia patients (330 microgram/1) and of 22 normal control subjects (164 microgram/1) (P less than 0.05 greater than 0.02). There was an inverse correlation between serum ferritin and Hb concentration in men with pernicious anaemia but not in women. Serum ferritin levels were lower in 10 of 13 patients studied after 24 h of vitamin B12 therapy and in all 13 studied at 48 h after therapy. The fall continued during the haematological response to therapy. It seems likely that serum ferritin reflects reticuloendothelial iron and the high levels in untreated megaloblastic anaemia are due to the shift in iron from Hb to reticuloendothelial stores. The wide variation in serum ferritin at any given Hb level presumably reflects variation in iron stores of the individual patient.

Topics: Aged; Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Child, Preschool; Female; Ferritins; Hemoglobins; Humans; Male; Middle Aged; Sex Factors; Vitamin B 12

Topics: Anemia, Megaloblastic; Anemia, Pernicious; Female; Folic Acid; Hematopoiesis; Humans; Ileum; Intrinsic Factor; Pregnancy; Vitamin B 12; Vitamin B 12 Deficiency

After introductory remarks on the physiology of blood during pregnancy the authors enter the two most frequent anaemias of pregnancy, which are evoked by iron deficiency and infection, as well as the megaloblastic, which are evoked by deficiency of folic acid--more infrequently also by deficiency of vitamin B12. The diagnostic and therapeutic principles are described in detail. It is only in short referred to the very rare haemolytic and toxic farms of anaemia, it is generally renounced to describe the haemorrhagic anaemia. A prophylaxis of the anaemia of pregnancy is intensely recommended.

Topics: Anemia; Anemia, Megaloblastic; Female; Folic Acid; Humans; Iron; Iron Deficiencies; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Hematologic; Vitamin B 12

We studied a six-month-old infant with severe megaloblastic anemia, coma and hyperpigmentation of the extremities. He was found to have methylmalonic aciduria (79 mumol per milligram of creatinine) and homocystinuria (0.85 mumol per milligram of creatinine). Additional biochemical abnormalities included cystathioninuria, glycinuria, methylcitric aciduria, 3-hydroxypropionic aciduria and formic aciduria. The concentration of vitamin B12 in the serum was 20 pg per milliliter. This severe nutritional deficiency was a consequence of inadequate intake, for the infant was exclusively breast-fed by a strictly vegetarian mother who manifested methylmalonic aciduria. Our observations emphasize the importance of educating strict vegetarians about the deficiency of vitamin B12 in their diets and the importance of vitamin B12 supplementation.

Topics: Adult; Amino Acid Metabolism, Inborn Errors; Anemia, Megaloblastic; Breast Feeding; Diagnosis, Differential; Diet, Vegetarian; Female; Homocystinuria; Humans; Infant; Infant Nutrition Disorders; Male; Methylmalonic Acid; Syndrome; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Megaloblastic; Bacteria; Humans; Intestine, Small; Penicillins; Vitamin B 12

Most, but not all, megaloblastic anemia is produced by "ineffective erythropoiesis" in the bone marrow due to either folic acid or vitamin B12 deficiency. In folic acid deficiency the cause frequently is inadequate dietary intake, whereas vitamin B12 deficiency is almost always conditioned by some specific type of malabsorption. Anemia with oval macrocytes, few reticulocytes, moderate leukopenia, and thrombocytopenia is typical of both. Aplastic anemia, refractory anemias with cellular marrow, preleukemia, aleukemia, and erythroleukemia may have somewhat similar blood findings but are usually recognizable from bone marrow biopsy. Decreased levels of folate or vitamin B12 are the most reliable criteria of megaloblastic anemia. With these available in advance, therapy with the appropriate vitamin can be begun at once. If serum levels are unavailable or available only in retrospect, initial treatment, especially of severe anemia, should be with both vitamins. Differentiation between folate and vitamin B12 deficiency is important but impossible by blood and bone marrow morphology alone. Thus, if serum levels are unavailable, the distinction must be made, sometimes retrospectively, on the basis of other laboratory examinations, such as gastric analysis, small-bowel x-ray films, and the Schilling test.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Folic Acid; Folic Acid Deficiency; Humans; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Megaloblastic; Anesthesia, Inhalation; Animals; Humans; Nitrous Oxide; Rats; Time Factors; Vitamin B 12

Topics: Adult; Anemia, Macrocytic; Anemia, Megaloblastic; Breast Feeding; Diet, Vegetarian; Female; Humans; Infant; Infant, Newborn; Male; Nutrition Disorders; Vitamin B 12

Topics: Anemia, Megaloblastic; Folic Acid; Humans; Radioimmunoassay; Reagent Kits, Diagnostic; Vitamin B 12

Topics: Adolescent; Anemia, Macrocytic; Anemia, Megaloblastic; Drug Therapy, Combination; Female; Folic Acid; Humans; Infant; Leucovorin; Vitamin B 12

Topics: Adenine Phosphoribosyltransferase; Anemia, Macrocytic; Anemia, Megaloblastic; Erythrocytes; Folic Acid; Humans; Hypoxanthine Phosphoribosyltransferase; Hypoxanthines; Purines; Reticulocytes; Ribose-Phosphate Pyrophosphokinase; Uric Acid; Vitamin B 12; Xanthines

Pancytopenia developed in four patients receiving postoperatively total parenteral nutrition (TPN). Symptoms and signs were related mainly to underlying bowel disease. Hematologic abnormalities, first noted from 4 to 7 weeks following institution of TPN, consisted of normocytic anemia (mean decrease in hemoglobin value, 2.2 g/dL), occasional macrocytes being noted, leukopenia (range of leukocyte counts, 1.2 to 3.6 X 10(9) L), some hypersegmented neutrophils being detected, and clinically significant thrombocytopenia (range of platelet counts, 25 to 52 X 10(9)/L). In all patients the bone marrow showed megaloblastic changes, with ring sideroblasts, although pyridoxine was included in the TPN regimens. Serum vitamin B12 values were normal in one patient and at the lower limit of normal in the other two patients in whom it was measured, while serum or erythrocyte folate values, or both, were reduced in three patients. Full hematologic response was observed in the four patients after folic acid replacement therapy; leukocytosis and thrombocytosis were noted in three. Thus, folic acid and possibly vitamin B12 should be added routinely to TPN regimens to prevent deficiency of either substance.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Folic Acid; Humans; Parenteral Nutrition; Vitamin B 12

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Cobamides; Humans; Malonates; Metabolism, Inborn Errors; Methylmalonic Acid; Vitamin B 12; Vitamin B 12 Deficiency

In most cases megaloblastic anaemias are the sequel of a deficiency of vitamin B12, more infrequently of a deficiency of folic acid of different etiology. Oriented to frequency and anamnesis the diagnostics follows the leading symptoms of pernicious anaemia (straw colour, glossitis, achlorhydria) and on the basis of special findings in the peripheral blood (hyperchromacia, megalocytosis, much decreased number of reticulocytes, increased iron and bilirubin level) it leads to the proved suspicion of a megaloblastic anaemia. This suspicion is ascertained by the investigation of the bone-marrow, with the help of aimed investigations the anaemia is further clarified differential-diagnostically. An unclear anaemia should not be treated ex juvantibus with vitamin B12 and/or folic acid. The therapy, always taking into consideration a possible basic disease, is carried out by parenteral application of vitamin B12, possibly in form of hydroxocobalamine or by folic acid. In persisting disturbance of the resorption of vitamin B12 on account of the threatening complication of a funicular spinal disease the long-term therapy must never be interrupted, unless in normal haematological findings.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Diagnosis, Differential; Humans; Intrinsic Factor; Vitamin B 12; Vitamin B 12 Deficiency

A patient with recurrent pulmonary abscess, weight loss, and alcoholism was found to have extremely high serum vitamin B12 and unsaturated vitamin B12-binding capacity (UBBC) levels. While transcobalamin (TC) II was also increased, most of his UBBC was due to an abnormal binding protein which carried greater than 80% of the endogenous vitamin B12 and was not found in his saliva, granulocytes, or urine. This protein was shown to be a complex of TC II and a circulating immunoglobulin (IgGkappa and IgGlambda). Each IgG molecule appeared to bind two TC II molecules. The reacting site did not interfere with the ability of TC II to bind vitamin B12, but did interfere with its ability to transfer the vitamin to cells in vitro. The site was not identical to that reacting with anti-human TC II antibody produced in rabbits. Because of this abnormal complex, 57Co-vitamin B12 injected intravenously was cleared slowly by the patient. However, no metabolic evidence for vitamin B12 deficiency was demonstrable, although the patient initially had megaloblastic anemia apparently due to folate deficiency. The course of the vitamin B12-binding abnormalities was followed over 4 yr and appeared to fluctuate with the status of the patient's illness. The IgG-TC II complex resembled one induced in some patients with pernicious anemia by intensive treatment with long-acting vitamin B12 preparations. The mechanism of induction of the antibody formation in our patient is unknown.

Topics: Adult; Alcoholism; Anemia, Megaloblastic; Antibodies; Blood Proteins; Humans; Male; Pneumonia; Transcobalamins; Vitamin B 12

In 11 patients with megaloblastic anemia, transfusion of packed erythrocytes or washed erythrocytes invariably resulted in a decline in plasma iron concentration to a range of 20-90 microgram/dl (3.6-16 mumol/l) after 36 to 48 hours. The same phenomenon was observed in two of six cases of ineffective erythropoiesis without megaloblastosis and in none of five cases of aplastic anemia. The observed changes did not result from a specific hematinic response or from iron uptake by a non-erythroid compartment. In megaloblastic anemia, alteration in marrow function in response to transfusion was reflected by plasma iron kinetics and serum lactate dehydrogenase values, which indicated marked reductions in both marrow hyperplasia and ineffective erythropoiesis. Transfusion in megalobastic anemia was also responsible for a 50% reduction in platelet count after 2 to 6 days. The significance of these changes is discussed.

Topics: Adult; Aged; Anemia; Anemia, Aplastic; Anemia, Macrocytic; Anemia, Megaloblastic; Blood Cell Count; Blood Platelets; Blood Transfusion; Female; Folic Acid; Humans; Iron; L-Lactate Dehydrogenase; Male; Middle Aged; Reticulocytes; Vitamin B 12

The vitamin B12 levels of cerebrospinal fluid were assayed microbiologically (Lactobacillus leichmannii method) using samples from 44 patients with various neurological disorders, 4 patients with megaloblastic anemia and 34 controls. Twenty-seven controls that did not receive vitamin B12 showed a mean cerebrospinal fluid vitamin B12 level of 21.5 pg/ml (range: 0-60). No decrease in cerebrospinal fluid vitamin B12 level was seen in patients with subacute myelo-optico-neuropathy (SMON). High levels of cerebrospinal fluid vitamin B12 were observed only in the patients receiving long term administration of the vitamin. Intrathecal administration of vitamin B12 caused only a slight increase in serum vitamin B12 level after four hours. The existence of blood brain barrier for vitamin B12 was suggested.

Topics: Anemia, Megaloblastic; Central Nervous System Diseases; Humans; Myelitis; Optic Neuritis; Syndrome; Vitamin B 12

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Female; Folic Acid; Folic Acid Deficiency; Humans; Infant, Newborn; Infant, Newborn, Diseases; Obstetric Labor Complications; Pregnancy; Pregnancy Complications, Hematologic; Vitamin B 12

We investigated the presence of vitamin B 12 analogues (cobamides) and the bacterial conversion of 57Co-B12 (vitamin B12 cyanocobalamin, [57Co]-CN-Cbl) into cobamides in the intestinal contents of four patients with bacterial overgrowth. The (57Co)-CN-Cbl bound to intrinsic factor was given orally. Jejunal contents were aspirated for 24 h and cultured aerobically and anaerobically. The CN-Cbl and cobamides were separated by electrophoresis and chromatography and identified by bioautography. Radioactivity of cobamide zones from duplicate chromatograms showed bacterial conversion of (57Co)-cn-cbl into cobamides. Cobamides ([Ade]CNCBA, [2-Me Ade] CNCba, [CN]2Cbi and factor E) were found in the intestinal contents in three of the four patients, and in two of three patients cobamides represented more than 25% of the administered CN-Cbl. Thus bacterial production of cobamides, both de novo and from ingested CN-Cbl bound to intrinsic factor, occurs in humans with bacterial overgrowth states and results in a significant loss of vitamin B12 to the host.

Topics: Anemia, Megaloblastic; Bacteria; Cobamides; Diverticulitis; Humans; Intestinal Obstruction; Intestine, Small; Malabsorption Syndromes; Vitamin B 12

Megaloblastic anaemia is due to a derangement of DNA synthesis caused by insufficient supply of one or other of the four deoxyribonucleoside triphosphate (dNTP) precursors of DNA synthesis or by direct inhibition of one or other DNA polymerase. Reduced supply of the pyrimidine deoxythymidine triphosphate (dTTP) may be caused by folate or vitamin B12 deficiencies or by the action of dihydrofolate reductase inhibitors (e.g. methotrexate, pyrimethamine or trimethoprim), all of which cause reduced supply of the coenzyme 5, 10 methylene tetrahydrofolate (pentaglutamate) needed for thymidylate synthetase. Reduced dTTP supply may also be caused by direct inhibition of thymidylate synthetase by 5-fluorouracil. Reduced supply of both purines, deoxyadenosine triphosphate (dATP) and deoxyguanosine triphosphate (dGTP), may be caused by hydroxyurea, 6-mercaptopurine (and probably by another purine antagonist azaserine), whilst reduced supply of both pyrimidine DNA precursors, dTTP and dCTP (deoxycytidine triphosphate) may be due to inherited orotic aciduria or to treatment with azauridine. Cytosine arabinoside directly inhibits DNA polymerase. DNA replication is a discontinuous process and a number of enzymes are concerned with different aspects of the process. The parental strands partly unwind and a large number of initiation points or origins are activated on both strands. A primer RNA is first synthesised using the parental strand of DNA as template. Fragments of new DNA are then synthesised on the parental DNA template, starting at the RNA primer, under the action of one or other DNA polymerase (probably gamma). The RNA primer is then removed and the gap left is filled by further DNA synthesis under the action of a different DNA polymerase (probably alpha). The fragments of new DNA are joined to give newly synthesised stretches of DNA (replicons) which are then liigated together to form bulk DNA of enormous molecular weight. It is suggested here that reduced supply of one or other of the four deoxyribonucleoside triphosphate (dNTP) during the 'S' phase of the cell cycle (due to vitamin B12 or folate deficiency, drug treatment or other congenital or acquired abnormality in synthesis of the dNTP) impairs the cell's ability to elongate newly initiated DNA fragments by preventing gap-filling, the polymerase needed for gap-filling requiring substantially greater concentrations of the deoxyribonucleoside triphosphates than the polymerase involved in chain initiation. C

Topics: Anemia, Megaloblastic; DNA; Folic Acid; Folic Acid Deficiency; Formiminoglutamic Acid; Glycine; Homocysteine; Humans; Methionine; Methylmalonyl-CoA Mutase; Nervous System Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Three cases of congenital selective malabsorption of vitamin B12 (Imerslund-Grasbeck syndrome) are presented. Pathophysiological aspected and clinical symptoms of this disease are discussed together with other megaloblastic anaemias in childhood caused by vitamin B12 deficiency.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Chronic Disease; Female; Humans; Infant; Intestinal Absorption; Recurrence; Syndrome; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Diet; Diphyllobothriasis; Diphyllobothrium; Finland; Humans; Vitamin B 12

Topics: Adolescent; Adult; Anemia, Megaloblastic; Animals; Antibody Formation; Child; Disease Models, Animal; DNA Replication; Folic Acid; Folic Acid Deficiency; Humans; Iron; Lectins; Lymphocytes; Middle Aged; Nutrition Disorders; Rats; Spleen; Thymus Gland; Transferrin; Vitamin B 12

Topics: Anemia, Megaloblastic; Cell Nucleus; DNA Replication; Fluorouracil; Folic Acid; Humans; Hydroxyurea; Lectins; Lymphocyte Activation; Lymphocytes; Thymine Nucleotides; Vitamin B 12

Thymidine kinase has been measured in phytohaemagglutinin (PHA)-stimulated lymphocytes from 13 normal subjects and eight patients with megaloblastic anaemia. The levels in normal subjects ranged from 0.20 to 2.10 units/mg protein (mean 0.903 units/mg protein) and in megaloblastic anaemia from 2.99 to 9.97 units/mg protein). All the patients showed raised levels of the enzyme which were partly but not completely reduced to normal by addition of folic acid in vitro. Vitamin B12 in vitro had a lowering effect in the five vitamin-B12-deficient patients and two patients with combined deficiencies but not in one 'pure' folate-deficient patient. Thymidine kinase activity was highest in the cells of the least anaemic patients, suggesting that the degree of anaemia in megaloblastic anaemia may be determined in part by the ability of the cells to utilize thymidine by the 'salvage' pathway when the de novo pathway of thymidylate synthesis is failing. The rise in thymidine kinase activity in megaloblastic anaemia is presumably due to induction of the enzyme. Addition of methotrexate or 5-fluorouracil, drugs known to inhibit de novo thymidylate synthesis, caused an increase in thymidine kinase activity in normal PHA-stimulated lymphocytes after 24 h (but not after 1 h) which could be completely blocked by addition of puromycin. Thymidine mono- and di-phosphate kinases were also measured in normal PHA-stimulated lymphocytes. The activities were substantially higher than that of thymidine kinase and their activities were unaffected by methotrexate addition.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Female; Fluorouracil; Folic Acid; Folic Acid Deficiency; Humans; Lectins; Lymphocyte Activation; Male; Methotrexate; Puromycin; Sonication; Thymidine Kinase; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Aminopterin; Anemia, Megaloblastic; Chemical Phenomena; Chemistry; Drug Combinations; Folic Acid; Humans; Methotrexate; Pyrimethamine; Sulfamethoxazole; Thrombocytopenia; Trimethoprim; Vitamin B 12

Topics: Anemia, Megaloblastic; Contraceptives, Oral; Contraceptives, Oral, Hormonal; Female; Humans; Intestinal Absorption; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Aged; Anemia, Megaloblastic; Chronic Disease; Female; Humans; Male; Middle Aged; Myeloproliferative Disorders; Polycythemia; Vitamin B 12

Reports concerning the interaction between steroidal contraceptives (the combined pill) and vitamins indicate that in users the mean serum-vitamin-A level is raised and the mean serum-vitamin-B2 (riboflavine), vitamin-B6 (pyridoxine), vitamine-C, folic-acid, and vitamin-B12 levels are reduced. Other vitamins have been insufficiently studied for comment. Biochemical evidence of co-enzyme deficiency has been reported for vitamin B2, vitamin B6, and folic acid. Clinical effects due to vitamin deficiency have been described for vitamin B6--namely, depression and impaired glucose tolerance. Folic-acid deficiency with megaloblastic anaemia has been reported in only 21 cases.

Topics: Anemia, Megaloblastic; Ascorbic Acid; Avitaminosis; Coenzymes; Contraceptives, Oral; Depression; Female; Folic Acid Deficiency; Glucose Tolerance Test; Humans; Pyridoxine; Riboflavin; Vitamin A; Vitamin B 12; Vitamin B 6 Deficiency

Transcobalamins are proteins which carry vitamin B12 and which are normally partly unsaturated. This study of transcobalamins was carried out in 17 subjects with megaloblastic anemia (12 true cases of pernicious anemia and 5 cases of folate deficiency). Among the latter, the transcobalamins were studied in 4 cases of pernicious anemia, before and after treatment with vitamin B12. The distribution of endogenous B12 was determined in four normal controls and two cases of pernicious anemia. This vitamin is normally distributed roughly equally between the three transcobalamins, whereas in B12 deficiency, T.C.2 is very unsaturated together with T.C.1 to a lesser degree. The latent fixation capacity of the serum is increased together with the latent fixation capacity of T.C. I and, above all, T.C. II but that of T.C. III is reduced in patients with pernicious anemia. In folate deficiency, only the latent fixation capacity of T.C. II is increased. When vitamin B12 is administered in physiological dosage, T.C. I becomes gradually saturated. In pharmacological dosage, total fixation capacity together with that of T.C. I and T.C. II become gradually reduced, but in spite of high levels of circulating B12, these proteins remain partially unsaturated. Various theories are suggested to explain the variations of these three transcobalamins in megaloblastic anemia but the problem is still unclear.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Blood Proteins; Folic Acid; Folic Acid Deficiency; Humans; Kinetics; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Because virtually all cases of vitamin B12 deficiency seen in this country are due to malabsorption, the availability of radioactive vitamin B12 for direct measurement of absorption of this essential nutrient has proved to be of great clinical value. These tests are useful not only in demonstrating vitamin B12 malabsorption but also often in defining the pathophysiological mechanism responsible for this abnormality. The urinary excretion test of Schilling remains the most useful test for vitamin B12 absorption. Minor precautions and modifications in technique make the test results more reliable and easier to interpret. The 8-hr plasma test for vitamin B12 absorption can no longer be considered acceptable. Some patients with vitamin B12 malabsorption have results in the normal range when studied by this method. Serum vitamin B12 assays utilizing radioactive vitamin B12 and the isotope dilution principle are not widely used and are useful screening tests. Low normal or borderline results observed in patients with clinical evidence suggestive of vitamin B12 deficiency should be interpreted with caution or confirmed by radioactive vitamin B12 absorption studies. Radioactive vitamin B12 can also be used for rapid, reliable assay of gastric intrinsic factor, antibody to intrinsic factor and unsaturated vitamin B12 serum. Methods using radioactive folate compounds for similar in vivo and in vitro studies are not yet applicable for routine use in nuclear medicine laboratories.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Cobalt Radioisotopes; Erythrocytes; Folic Acid; Folic Acid Deficiency; Humans; Intestinal Absorption; Intrinsic Factor; Radioimmunoassay; Radioisotope Dilution Technique; Schilling Test; Tritium; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Child; Chronic Disease; Follow-Up Studies; Humans; Male; Recurrence; Syndrome; Vitamin B 12

We have described a case of chronic arsenic intoxication associated with pancytopenia and megaloblastic erythropoiesis. The patient had the typical laboratory manifestations of effective erythorpoiesis due to a megaloblastic process, including macroovalocytes, mild pancytopenia, low reticulocyte index, increased marrow cellularity with erythroid hyperplasia, and morphologic evidence of megaloblastic maturation in the marrow. The patient's serum folate and vitamin B12 were normal, and the anemia regressed without therapy. Our case suggests that the combination of megaloblastosis with normoblastic or megaloblastic karyorrhexis,should raise the suspicion of arsenic intoxication in the mind of the observer. In addition, arsenic should be added to the list of agents causing a reversible megaloblastic anemia.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Arsenic; Arsenic Poisoning; Bone Marrow Examination; Erythropoiesis; Folic Acid; Hair; Humans; Keratosis; Liver; Male; Middle Aged; Nails; Neural Conduction; Neurologic Manifestations; Remission, Spontaneous; Reticulocytes; Vitamin B 12

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Gastrectomy; Humans; Ileum; Intrinsic Factor; Malabsorption Syndromes; Metabolism, Inborn Errors; Schilling Test; Time Factors; Vitamin B 12

Topics: Administration, Oral; Anemia, Macrocytic; Anemia, Megaloblastic; Diagnosis, Differential; DNA; Electroencephalography; Electromyography; Folic Acid Deficiency; Humans; Mental Disorders; Syndrome; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Deficiency

The return of the MCV to normal after treatment in megaloblastic anaemia follows a biphasic pattern. The initial more rapid decline in MCV is due to disappearance of pretreatment macrocytes from the circulation and the rate of fall is determined by their mean cell life. The second slower component is probably due to a mixture of pretreatment macrocytes and new macrocytes, the result of a young red cell population. The MCV often returned to normal most rapidly in the most severely megaloblastic patients due to a very short mean red cell life span. However, there was no significant correlation between either initial MCV or red cell count and the time after treatment for a return of a normal MCV.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Erythrocytes, Abnormal; Folic Acid; Humans; Hydroxocobalamin; Time Factors; Vitamin B 12

The present study has examined the relationship and significance of hypocholesterolaemia to anaemia and to the red cell. The level of plasma cholesterol is closely related to haematocrit levels both initially and throughout the course of the anaemias associated with hypocholesterolaemia. The association is maintained, regardless of the cause of the haematocrit change, i.e. transfusion or response to treatment. Hypocholesterolaemia does not affect the red cell, i.e. its survival, cholesterol concentration or osmotic fragility and occurs in a diverse group of anaemias. As such, it is not causally related to anaemia. The changes in plasma cholesterol are most likely related to its 'redistribution' or to plasma 'dilution', with contributory factors occurring. The presence of anaemia, even to a modest degree, would be important to consider when comparing cholesterol levels between groups of individuals.

Topics: Anemia; Anemia, Aplastic; Anemia, Megaloblastic; Anemia, Sickle Cell; Blood Transfusion; Cholesterol; Erythrocyte Aging; Erythrocytes; Folic Acid; Hematocrit; Humans; Liver Cirrhosis; Osmotic Fragility; Spherocytosis, Hereditary; Splenectomy; Vitamin B 12

Two cases of Imerslund's disease are reported, with special reference to the treatment with vitamin B 12. Data suggest that mean corpuscular volume and urinary excretion of methylmalonic acid are the most sensitive parameters to follow the effect of the treatment and predict the relapse.

Topics: Adult; Anemia, Macrocytic; Anemia, Megaloblastic; Child; Female; Humans; Malabsorption Syndromes; Male; Vitamin B 12; Vitamin B 12 Deficiency

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Adult; Anemia, Macrocytic; Anemia, Megaloblastic; Ascorbic Acid Deficiency; Child; Female; Folic Acid; Folic Acid Antagonists; Folic Acid Deficiency; Humans; Infant; Intestinal Diseases; Malabsorption Syndromes; Nutritional Physiological Phenomena; Nutritional Requirements; Orotic Acid; Pregnancy; Pregnancy Complications; Tetrahydrofolate Dehydrogenase; Thiamine Deficiency; Transferases; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin E Deficiency

Topics: Agammaglobulinemia; Alpha-Globulins; Anemia, Megaloblastic; Beta-Globulins; Blood Cell Count; Blood Platelets; Blood Transfusion; Bone Marrow; Bone Marrow Examination; Consanguinity; Humans; Infant, Newborn; Infant, Newborn, Diseases; Leukocyte Count; Male; Neutrophils; Pedigree; Protein Binding; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Administration, Oral; Anemia, Megaloblastic; Child; Child, Preschool; Cobalt Radioisotopes; Erythrocytes; Female; Folic Acid; Folic Acid Deficiency; Humans; Ileum; Infant; Injections; Intestinal Absorption; Male; Postoperative Complications; Puberty; Vitamin B 12; Whole-Body Counting

Topics: Agricultural Workers' Diseases; Anemia; Anemia, Hypochromic; Anemia, Megaloblastic; Diet; Folic Acid; Hookworm Infections; Iron; Sanitation; Socioeconomic Factors; Sri Lanka; Vitamin B 12

Topics: Adolescent; Anemia, Macrocytic; Anemia, Megaloblastic; Drug Combinations; Female; Folic Acid Deficiency; Hemorrhage; Humans; Infectious Mononucleosis; Pyrimethamine; Sulfamethoxazole; Trimethoprim; Vitamin B 12

Topics: Adult; Anemia, Megaloblastic; Female; Folic Acid; Folic Acid Deficiency; Hemoglobinopathies; Humans; Pregnancy; Thalassemia; Vitamin B 12

Topics: Administration, Oral; Adolescent; Adult; Anemia, Macrocytic; Anemia, Megaloblastic; Child; Diet Therapy; Female; Folic Acid; Folic Acid Deficiency; Hemoglobins; Humans; Injections, Intramuscular; Intestinal Absorption; Intestine, Small; Male; Middle Aged; Nucleoproteins; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Achlorhydria; Anemia, Megaloblastic; Anorexia Nervosa; Body Weight; Bone Marrow Cells; Celiac Disease; Diarrhea; Gastritis; Hemoglobinometry; Humans; Jejunum; Malabsorption Syndromes; Sprue, Tropical; Tetracycline; Vitamin B 12; Zimbabwe

Topics: Anemia; Anemia, Aplastic; Anemia, Hemolytic; Anemia, Hypochromic; Anemia, Megaloblastic; Anemia, Sideroblastic; Blood Transfusion; Diet Therapy; Female; Folic Acid; Humans; Iron; Kidney Diseases; Male; Postgastrectomy Syndromes; Pregnancy; Pregnancy Complications, Hematologic; Vitamin B 12

Topics: Adult; Anemia, Macrocytic; Anemia, Megaloblastic; Edema; Female; Folic Acid; Humans; Lactation; Malabsorption Syndromes; Pregnancy; Pregnancy Complications, Hematologic; Vitamin B 12

The blood concentrations of vitamin B12 and folate, which are very useful in diagnosis of megaloblastic anemia and of these factors' dificiencies, are actually measured by precise, rapid, and specific competitive binding radioassays. Futher clinical advantages can be reached with the application of other in vitro radioisotope techniques, such as radioassay of IF, of antibodies anti-IF, of transcobalamins, and of FABP (folic acid binding protein). The major impact of the vitamin B12, folates and other related radioassays has been to permit more Hospitals and laboratories to do these determinations, replacing the more time-consuming, relatively imprecise, and often artifactual microbiological assays.

Topics: Anemia, Megaloblastic; Anemia, Sideroblastic; Antibodies; FIGLU Test; Folic Acid; Folic Acid Deficiency; Intrinsic Factor; Radioimmunoassay; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Heinz Bodies; Humans; Postoperative Complications; Splenectomy; Vitamin B 12

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Bone Marrow Examination; Child; Fluids and Secretions; Folic Acid; Humans; Infant; Metabolism, Inborn Errors; Nucleosides; Orotic Acid; Prognosis; Purine-Pyrimidine Metabolism, Inborn Errors; Pyridoxine; Thyroxine; Uridine; Urine; Vitamin B 12

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Black People; Diagnosis; Diverticulum; Drug Therapy; Duodenal Diseases; Geriatrics; Humans; Jejunum; Vitamin B 12

Folic acid deficiency with the picture of a megaloblastic bone marrow may develop in haemolytic anaemia, and, on the other hand, both vitamin B(12) and folic acid deficiency may produce signs of haemolysis. As the correct interpretation of a positive antiglobulin reaction associated with megaloblastic erythropoiesis is particularly important, the effect of deficiency of vitamin B(12) and folic acid on the results of the test was investigated in 32 patients with vitamin B(12) or folic acid deficiency and a positive antiglobulin reaction was obtained in ten. There was no correlation between the result of the test and the degree of anaemia, and there was no significant difference between the incidence of positive results associated with deficiency of vitamin B(12) or folic acid. In determining the significance of a positive result, the time interval before agglutination occurs is sometimes of greater value than the strength of the reaction or the result of the gamma globulin neutralization test.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Antibodies, Anti-Idiotypic; Coombs Test; Folic Acid; Folic Acid Deficiency; gamma-Globulins; Hemagglutination Inhibition Tests; Humans; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Drug Therapy; Folic Acid; Hemochromatosis; Humans; Vitamin B 12

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Blood Chemical Analysis; Diet; Diet Therapy; Drug Therapy; FIGLU Test; Folic Acid; Folic Acid Deficiency; Geriatrics; Hematinics; Hemochromatosis; Humans; Liver Cirrhosis; Liver Function Tests; Metabolism; Vitamin B 12

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Diverticulum; Drug Therapy; Duodenal Diseases; Humans; Intestines; Metronidazole; Tetracycline; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Anemia, Pernicious; Blood Chemical Analysis; Hematinics; Humans; Vitamin B 12; Vitamins

Topics: Anemia; Anemia, Hypochromic; Anemia, Macrocytic; Anemia, Megaloblastic; Blood; Drug Therapy; Folic Acid; Hematopoiesis; Humans; Vitamin B 12

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Female; Folic Acid; Humans; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic; Vitamin B 12

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Barbiturates; Biological Assay; Blood Chemical Analysis; Folic Acid; Folic Acid Deficiency; Geriatrics; Glutamates; Toxicology; Urine; Vitamin B 12; Vitamin B 12 Deficiency

There is a significant fall in the serum folic acid level during pregnancy, reaching its lowest level at term. This is most pronounced in twin pregnancies. A similar but less spectacular fall occurs in the vitamin B(12) concentration. In megaloblastic anaemia both folic acid and vitamin B(12) levels are lower than in other pregnant women. The degree of megaloblastic change in the bone marrow, as measured by the type and number of megaloblasts, is reflected in the vitamin levels, cases with florid megaloblastosis showing the most marked depression of vitamin B(12) and folic acid activity. Although there is a significant difference in the mean folic acid levels between megaloblastic and normoblastic pregnant women, a considerable overlap exists between individual values in the two groups. When the labile folic-acid factor is determined separately the test becomes much more specific. In the present series, all cases of megaloblastic anaemia yielded labile-factor levels below 1.0 mmug. per ml., while a similar value was encountered in only one of 35 normal pregnancies. In five women with megaloblastic anaemia the vitamin B(12) concentration was less than 100 mumug. per ml. but rose to normal levels on folic acid therapy alone.

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Biological Assay; Blood; Bone Marrow; Bone Marrow Examination; Classification; Euglena; Female; Folic Acid; Humans; Lactobacillus; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic; Twins; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Celiac Disease; Classification; Folic Acid; Folic Acid Deficiency; Humans; Japan; Metabolism; Physiology; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Celiac Disease; Deficiency Diseases; Diagnosis; Female; Folic Acid; Humans; Intrinsic Factor; Malabsorption Syndromes; Physiology; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic; Sprue, Tropical; Vitamin B 12

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Brain Diseases; Cysticercosis; Drug Therapy; Epilepsy; Folic Acid; Humans; Iatrogenic Disease; Phenobarbital; Phenytoin; Primidone; Spinal Cord; Toxicology; Vitamin B 12

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Blood Platelet Disorders; Drug Therapy; Epilepsy; Female; Folic Acid; Hemorrhage; Humans; Phenobarbital; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic; Primidone; Thrombocytopenia; Toxicology; Vitamin B 12

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Diverticulum; Drug Therapy; Escherichia coli Infections; Geriatrics; Humans; Intestinal Absorption; Intestine, Small; Intestines; Tetracycline; Vitamin B 12

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Celiac Disease; Diverticulum; Drug Therapy; Geriatrics; Humans; Intestinal Diseases; Intestine, Small; Intestines; Pain; Steatorrhea; Tetracycline; Toxicology; Vitamin B 12

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Folic Acid; Folic Acid Deficiency; Humans; Vitamin B 12; Vitamin B 12 Deficiency; Yeast, Dried

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Folic Acid; Humans; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Blood Cell Count; Deficiency Diseases; Drug Therapy; Female; Folic Acid; Folic Acid Deficiency; Humans; Intrinsic Factor; Malabsorption Syndromes; Metabolism; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Ascorbic Acid; Folic Acid; Humans; Metabolism; Vitamin B 12

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Drug Therapy; Humans; Polycythemia Vera; Vitamin B 12

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Blood; Blood Cell Count; Geriatrics; Glutamates; Iron; Neutrophils; Pyrimethamine; Toxicology; Urine; Vitamin B 12; Vitamin B Complex

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Drug Therapy; Gastrectomy; Humans; Intrinsic Factor; Vitamin B 12

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Folic Acid; Hematinics; Humans; Incidence; Vitamin B 12

Topics: Anemia, Megaloblastic; Hematinics; Humans; Schilling Test; Vitamin B 12

The importance of deficiency of the folic acid group of compounds (folates) in the pathogenesis of nutritional anaemias is receiving increasing recognition. There is evidence that the megaloblastic anaemias, due to either vitamin B(12) or folate deficiency, may be the cause of widespread morbidity in malnourished populations. It was therefore considered timely to review certain aspects of the role of folates in megaloblastic anaemia, with special reference to the dietary intake in relation to human requirements, and the recognition of folate deficiency in man.

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Folic Acid; Folic Acid Deficiency; Humans; Male; Vitamin A Deficiency; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Corrinoids; Diagnosis, Differential; Humans; Vitamin B 12

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Corrinoids; Folic Acid; Humans; Prednisolone; Vitamin B 12

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Corrinoids; Humans; Vitamin B 12; Vitamins

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Folic Acid; Histidine; Humans; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Diet, Vegetarian; Humans; Vitamin B 12

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Ascorbic Acid; Ascorbic Acid Deficiency; Folic Acid; Humans; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Ascorbic Acid; Folic Acid; Geriatrics; Hemoglobinometry; Humans; Reticulocytes; Vitamin B 12; Vitamin B Deficiency

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Blood Chemical Analysis; Diagnosis; Folic Acid; Humans; L-Lactate Dehydrogenase; Vitamin B 12

Topics: Amobarbital; Anemia, Macrocytic; Anemia, Megaloblastic; Anticonvulsants; Barbiturates; Epilepsy; Folic Acid; Humans; Metabolism; Phenobarbital; Phenytoin; Primidone; Toxicology; Vitamin B 12

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Humans; Pelger-Huet Anomaly; Sex Chromatin; Vitamin B 12

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Black People; Ethnology; Humans; India; South Africa; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Bone Marrow Examination; Fatty Liver; Folic Acid; Gastrectomy; Hemochromatosis; Hemosiderosis; Humans; Iron; Liver Cirrhosis; Vitamin B 12; Vitamin B Deficiency

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Humans; Hypothyroidism; Postgastrectomy Syndromes; Protein Deficiency; Thyroid Hormones; Vitamin B 12

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Ascorbic Acid; Asian People; Blood Chemical Analysis; Bone Marrow Examination; Dietary Carbohydrates; Dietary Proteins; Folic Acid; Folic Acid Deficiency; Leucovorin; Lipids; Myanmar; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Humans; Infant; Infant Nutrition Disorders; Kwashiorkor; Protein-Energy Malnutrition; Vitamin B 12

Topics: Adult; Anemia; Anemia, Megaloblastic; Folic Acid; Glutamates; Humans; Thiamine; Vitamin B 12

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Corrinoids; Folic Acid; Humans; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Anemia, Pernicious; Folic Acid; Radioisotopes; Vitamin B 12

In 21 patients with megaloblastic anaemia associated with the tropical malabsorption syndrome serum vitamin B(12) levels have been measured serially before and during parenteral folic acid therapy. In 11 patients there was a significant rise in serum B(12) levels, reaching a peak three to 17 days after starting the folic acid. In three of these cases, absorption of labelled B(12) was the same before and after the administration of folic acid. In two cases there was a fall in serum B(12) levels and in seven there was no change. In one case small amounts of folic acid produced no change in serum B(12) levels, whereas larger doses produced a prompt but transient rise.

Topics: Anemia; Anemia, Megaloblastic; Folic Acid; Humans; Seasons; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Anticonvulsants; Corrinoids; Hematinics; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Celiac Disease; Folic Acid; Humans; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Child; Humans; Infant; Proteinuria; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia; Anemia, Megaloblastic; Hematinics; Humans; Vitamin B 12; Vitamin B Complex; Vitamins

The absorption of (60)CoB(12) has been studied in a group of patients suffering from megaloblastic anaemia associated with pregnancy and in a control group. The mean urinary excretion of (60)CoB(12) in the patients with megaloblastic anaemia is not significantly different from that of the control group. Five of the 30 patients showed a value towards the lower limit of normal, but the serum vitamin B(12) content in this group was within the normal range. Malabsorption of vitamin B(12) does not appear to play a significant role in the pathogenesis of this form of megaloblastic anaemia.

Topics: Anemia; Anemia, Megaloblastic; Female; Humans; Pregnancy; Pregnancy Complications; Reference Values; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Folic Acid; Humans; Vitamin B 12

Urinary amino-acid chromatograms from 23 patients with megaloblastic anaemia have been studied before and after therapy. The most consistent abnormality was an increased taurine or increased taurine/glycine ratio. This was not related directly to deficiency of vitamin B(12) or folic acid or to the degree of anaemia.

Topics: Amino Acids; Anemia; Anemia, Megaloblastic; Folic Acid; Humans; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Corrinoids; Hematinics; Humans; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Anticonvulsants; Corrinoids; Hematinics; Humans; Hydantoins; Phenobarbital; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Folic Acid Deficiency; Humans; Vitamin B 12; Vitamin B Complex

Topics: Anemia; Anemia, Megaloblastic; Anti-Bacterial Agents; Humans; Liver Extracts; Prednisone; Tetracycline; Vitamin B 12; Vitamin B Complex

Topics: Anemia, Megaloblastic; Corrinoids; Erythroblasts; Gastrectomy; Hematinics; Humans; Vitamin B 12

Topics: Aerosols; Anemia; Anemia, Megaloblastic; Blood Platelets; Corrinoids; Humans; Reticulocytes; Vitamin B 12; Vitamin B Complex

Topics: Anemia; Anemia, Megaloblastic; Child; Hematinics; Humans; Infant; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Humans; Regression Analysis; Schilling Test; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Female; Hematinics; Humans; Postpartum Period; Pregnancy; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Hematinics; Humans; Orotic Acid; Riboflavin; Vitamin B 12; Vitamin B Complex

Topics: Anemia; Anemia, Megaloblastic; Humans; Thromboplastin; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Humans; Primidone; Vitamin B 12; Vitamin B Complex

Topics: Anemia; Anemia, Megaloblastic; Corrinoids; Folic Acid; Hematinics; Humans; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Anemia, Pernicious; Corrinoids; Humans; Vitamin B 12

Topics: Administration, Oral; Anemia; Anemia, Megaloblastic; Humans; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Gastric Juice; Intrinsic Factor; Vitamin B 12; Vitamin B Complex

Topics: Anemia; Anemia, Megaloblastic; Corrinoids; Hematinics; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Constriction, Pathologic; Hematinics; Intestines; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Female; Humans; Postpartum Period; Pregnancy; Pregnancy Complications; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Folic Acid; Humans; Vitamin B 12; Vitamin B Complex

Topics: Anemia; Anemia, Megaloblastic; Gastric Juice; Hematinics; Vitamin B 12

Two of the mechanisms for vitamin B(12) deficiency, leading to megaloblastic anemia, are the result of surgically produced abnormalities of the gastrointestinal tract. The basic mechanism is different for each lesion. Total gastrectomy results in complete lack of intrinsic factor which is necessary for vitamin B(12) absorption. It is believed that if patients survive long enough and are not given prophylactic vitamin B(12) therapy, all would develop megaloblastic anemia. Intestinal anastomosis leading to stasis of intestinal contents, with overgrowth of bacteria may cause vitamin B(12) deficiency through bacterial interference with the utilization of vitamin B(12). Use of radioactive vitamin B(12) (cobalt(60)-labeled B(12)) has led to a better understanding of the pathogenesis of both types of megaloblastic anemia. The radioactive vitamin provides a useful tool for study of its absorption from the gastrointestinal tract.

Topics: Anastomosis, Surgical; Anemia; Anemia, Megaloblastic; Antibiosis; Digestive System Abnormalities; Gastrectomy; Gastrointestinal Tract; Hematinics; Humans; Intrinsic Factor; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex; Vitamins

Topics: Anemia; Anemia, Megaloblastic; Black People; Blood; Hematinics; Humans; Penicillins; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Humans; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Female; Humans; Pregnancy; Pregnancy Complications; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Gastric Juice; Hematinics; Intrinsic Factor; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Folic Acid; Gastric Juice; Hematinics; Humans; Intrinsic Factor; Leucovorin; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Blood; Folic Acid; Hematinics; Humans; Urinary Tract; Urine; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Hematinics; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Bacteriology; Blood; Hematinics; Humans; Intestines; Penicillins; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Female; Humans; Pregnancy; Pregnancy Complications; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Anemia, Pernicious; Bone Marrow; Folic Acid; Humans; Nucleic Acids; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Blood; Corrinoids; Folic Acid; Hematinics; Humans; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Biopsy; Diagnosis, Differential; Humans; Stomach; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia; Anemia, Megaloblastic; Colon; Corrinoids; Humans; Intestine, Small; Intestines; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Folic Acid; Hematinics; Humans; Leucovorin; Vitamin B 12; Vitamin B Complex

Topics: Anemia; Anemia, Megaloblastic; Child; Folic Acid; Humans; Infant; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Folic Acid; Hematinics; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Diagnosis, Differential; Hematinics; Humans; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Bone Marrow; Folic Acid; Humans; In Vitro Techniques; Uracil; Vitamin B 12; Vitamin B Complex

Topics: Anemia; Anemia, Megaloblastic; Hematinics; Penicillins; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Anemia, Pernicious; Arylsulfonates; Humans; Liver Extracts; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Bone Marrow; Folic Acid; Humans; In Vitro Techniques; Uracil; Vitamin B 12; Vitamin B Complex

Topics: Anemia; Anemia, Megaloblastic; Child; Hematinics; Humans; Infant; Vitamin B 12; Vitamin B Complex

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Animals; Diet; Feces; Folic Acid; Haplorhini; Hematinics; Humans; Liver; Scurvy; Vitamin B 12; Vitamin B Complex

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Hematinics; Humans; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Anemia, Pernicious; Corrinoids; Folic Acid; Vitamin B 12

The newer hematinics are merely refinements of preexisting forms of treatment, but they have aided particularly in a better understanding of the deficiency states. The intrinsic factor of Castle has not been isolated from the gastric juice, and the interrelationships of this substance with the extrinsic factor (vitamin B(12)) and folic acid have not been defined at this time. Vitamin B(12) appears to be the active principle of refined liver extract and alone is probably adequate treatment for pernicious anemia. The other varieties of megaloblastic anemia may result from deficiency of vitamin B(12) or folic acid, although generally treatment with the latter brings about complete and lasting remission. The use of multihematinics and multivitamin preparations containing folic acid is to be condemned, particularly because of the possibility of their obscuring anemia and thwarting diagnosis of pernicious anemia until neurologic complications have taken place. Saccharated oxide of iron is a relatively safe preparation for intravenous administration, but the indications for its use are few. Because the body has no mechanism for iron excretion, only the amount of iron necessary to make up a deficiency should be given, although there is no definite evidence that hemochromatosis results from overdosage.

Topics: Anemia; Anemia, Iron-Deficiency; Anemia, Megaloblastic; Anemia, Pernicious; Folic Acid; Hematinics; Humans; Intrinsic Factor; Iron; Iron Compounds; Iron Metabolism Disorders; Liver Extracts; Substance-Related Disorders; Vitamin B 12; Vitamins

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Corrinoids; Folic Acid; Humans; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Folic Acid; Humans; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Anemia, Pernicious; beta-Thalassemia; Corrinoids; Folic Acid; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Anemia, Pernicious; Body Fluids; Humans; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Animals; Folic Acid; Goats; Humans; Milk; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Corrinoids; Folic Acid; Gastrectomy; Humans; Vitamin B 12; Vitamin B Complex

Topics: Anemia; Anemia, Megaloblastic; Corrinoids; Folic Acid; Humans; Leucovorin; Vitamin B 12; Vitamin B Complex

Topics: Anemia; Anemia, Megaloblastic; Anemia, Pernicious; Folic Acid; Humans; Vitamin B 12; Vitamin B Complex

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Humans; Pregnancy; Pregnancy Complications; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Anemia, Pernicious; Corrinoids; Vitamin B 12

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Ascorbic Acid; Humans; Pregnancy; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Corrinoids; Folic Acid; Hematinics; Humans; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; beta-Thalassemia; Folic Acid; Hematinics; Humans; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Anemia, Pernicious; Anti-Bacterial Agents; Antibiotics, Antitubercular; beta-Thalassemia; Humans; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Humans; Vitamin B 12; Vitamin B Complex

Topics: Anemia; Anemia, Megaloblastic; Anemia, Pernicious; Folic Acid; Humans; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Humans; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Anemia, Pernicious; Hematinics; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Hematinics; Vitamin B 12; Vitamin B Complex

Topics: Anemia; Anemia, Megaloblastic; Corrinoids; Female; Folic Acid; Hematinics; Humans; Postpartum Period; Pregnancy; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Anemia, Pernicious; Folic Acid; Hematinics; Thymine; Tissue Donors; Uracil; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Folic Acid; Humans; Liver Extracts; Pregnancy; Vitamin B 12; Vitamins

Topics: Anemia; Anemia, Megaloblastic; Humans; Spinal Cord; Subacute Combined Degeneration; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Anemia, Pernicious; Humans; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Anemia, Pernicious; Hematinics; Vitamin B 12

Topics: Anemia; Anemia, Megaloblastic; Child; Humans; Infant; Vitamin B 12; Vitamin B Complex; Vitamins

Topics: Anemia; Anemia, Megaloblastic; Humans; Vitamin B 12