intrinsic-factor and 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

The usual dietary sources of vitamin B12 are animal-source based foods, including meat, milk, eggs, fish, and shellfish, although a few plant-based foods such as certain types of dried lavers (nori) and mushrooms contain substantial and considerable amounts of vitamin B12, respectively. Unexpectedly, detailed characterization of vitamin B12 compounds in foods reveals the presence of various corrinoids that are inactive in humans. The majority of edible blue-green algae (cyanobacteria) and certain edible shellfish predominately contain an inactive corrinoid known as pseudovitamin B12. Various factors affect the bioactivity of vitamin B12 in foods. For example, vitamin B12 is partially degraded and loses its biological activity during cooking and storage of foods. The intrinsic factor-mediated gastrointestinal absorption system in humans has evolved to selectively absorb active vitamin B12 from naturally occurring vitamin B12 compounds, including its degradation products and inactive corrinoids that are present in daily meal foods. The objective of this review is to present up-to-date information on various factors that can affect the bioactivity of vitamin B12 in foods. To prevent vitamin B12 deficiency in high-risk populations such as vegetarians and elderly subjects, it is necessary to identify plant-source foods that contain high levels of bioactive vitamin B12 and, in conjunction, to prepare the use of crystalline vitamin B12-fortified foods.

Topics: Agaricales; Aged; Corrinoids; Cyanobacteria; Diet; Diet, Vegetarian; Food; Food Handling; Food, Fortified; Hot Temperature; Humans; Intestinal Absorption; Intrinsic Factor; Shellfish; 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 discovery of vitamin B(12), the elucidation of its role in metabolism, and the effects and treatment of its deficiency occurred in distinct phases over more than 100 years, and it was the subject of two separate Nobel Prizes. The valuable contribution of clinical reports and studies of patients with pernicious anemia throughout the 19th century resulted in enough clinical definition to allow Minot and Murphy to put together the first hallmark study on treatment of the condition, leading them to a Nobel Prize. These researchers were not the first to suggest that an inadequacy of nutrients was the cause of pernicious anemia, but their particular input was a carefully designed intervention in well-characterized pernicious anemia patients, of a special diet containing large amounts of liver. They found consistent improvement in the clinical and blood status of all subjects, most of whom remained on remission indefinitely. After the successful intervention studies, the next advance was made by Castle who discovered that a gastric component, which he called intrinsic factor, was missing in pernicious anemia. Many years later, intrinsic factor was found to be a glycoprotein that formed a complex with vitamin B(12), promoting its absorption through ileal receptors. The vitamin was isolated by two groups simultaneously and was crystallized and characterized in the laboratory of Dorothy Hodgkin, contributing to her Nobel Prize in 1964. Subsequently, the various biochemical roles of vitamin B(12) were elucidated, including its important interaction with folate and their common link with megaloblastic anemia. Many of the early clinical studies recognized that vitamin B(12) deficiency also caused a severe neuropathy leading to paralysis and death, while post mortem analysis demonstrated spinal cord demyelination. Vitamin B(12) is still the subject of intense research and, in particular, its role in preventing these irreversible neurological lesions remains unclear.

Topics: Anemia, Pernicious; Animals; Gastric Mucosa; History, 20th Century; Humans; Intrinsic Factor; Nobel Prize; Vitamin B 12; Vitamin B 12 Deficiency

The haematological and neurological consequences of cobalamin deficiency define the essential role of this vitamin in key metabolic reactions. The identification of cubilin-amnionless as the receptors for intestinal absorption of intrinsic factor-bound cobalamin and the plasma membrane receptor for cellular uptake of transcobalamin bound cobalamin have provided a clearer understanding of the absorption and cellular uptake of this vitamin. As the genes involved in the intracellular processing of cobalamins and genetic defects of these pathways are identified, the metabolic disposition of cobalamins and the proteins involved are being recognized. The synthesis of methylcobalamin and 5'-deoxyadenosylcobalamin, their utilization in conjunction with methionine synthase and methylmalonylCoA mutase, respectively, and the metabolic consequences of defects in these pathways could provide insights into the clinical presentation of cobalamin deficiency.

Topics: Biological Transport, Active; Humans; Intestinal Absorption; Intrinsic Factor; Metabolism, Inborn Errors; Receptors, Cell Surface; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

The objective of this review is to evaluate the usefulness of oral cobalamin (vitamin B12) treatment.. PubMed was systematically searched for English and French articles published from January 1990 to January 2007.. Prospective randomized studies (n = 3), a systematic review by the Cochrane group (n = 1) and prospective studies in well-determined population (n = 5) provide evidence that oral cyanocobalamin therapy may adequately treat cobalamin deficiency in elderly patients. However, the current literature may not suggest a strategy in terms of the form (hydroxy- or cyanocobalamin), frequency and duration of the treatment.. This present review confirms the previously reported efficacy of oral cyanocobalamin treatment in elderly patients.

Topics: Administration, Oral; Aged; Diet; Dietary Supplements; Humans; Intrinsic Factor; Malabsorption Syndromes; Prospective Studies; Randomized Controlled Trials as Topic; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Biological Transport; Folic Acid; Humans; Hyperhomocysteinemia; Intrinsic Factor; Metabolism, Inborn Errors; Methylenetetrahydrofolate Reductase (NADPH2); Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Autoantibodies; Biomarkers; Humans; Immunologic Tests; Intestinal Absorption; Intrinsic Factor; Vitamin B 12; Vitamin B 12 Deficiency

The primary function of cobalamin (Cbl; vitamin B12) is the formation of red blood cells and the maintenance of a healthy nervous system. Before cells can utilise dietary Cbl, the vitamin must undergo cellular transport using two distinct receptor-mediated events. First, dietary Cbl bound to gastric intrinsic factor (IF) is taken up from the apical pole of ileal epithelial cells via a 460 kDa receptor, cubilin, and is transported across the cell bound to another Cbl-binding protein, transcobalamin II (TC II). Second, plasma TC II-Cbl is taken up by cells that need Cbl via the TC II receptor (TC II-R), a 62 kDa protein that is expressed as a functional dimer in cellular plasma membranes. Human Cbl deficiency can develop as a result of acquired or inherited dysfunction in either of these two transmembrane transport events. This review focuses on the biochemical, cellular and molecular aspects of IF and TC II and their cell-surface receptors.

Topics: Cell Membrane; Humans; Intestinal Absorption; Intrinsic Factor; Receptors, Cell Surface; Structure-Activity Relationship; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

The classic workup of a patient for possible PA is revisited in light of the vanishing Schilling test. The vagaries of testing for B12 and blocking antibodies are reexamined. The advantages and disadvantages of newer tests such as MMA and serum gastrin levels are catalogued. At this juncture in the evolution of new test strategies, there is a considerable controversy regarding the significance of high MMA levels in the face of normal B12 levels, particularly in the elderly. Hopefully, this controversy will soon be resolved and the newer crop of tests will be proven and accepted in the workplace. Still, the words of Alexander Pope spring to mind: "Be not the first by whom the new are tried, Nor yet the last to lay the old aside."

Topics: Anemia, Pernicious; Antibodies, Blocking; Gastrins; Humans; Intrinsic Factor; Methylmalonic Acid; Pathology, Clinical; Schilling Test; Vitamin B 12; Vitamin B 12 Deficiency

Transcobalamin II (TC II), a nonglycoprotein secretory protein of molecular mass 43 kDa, and its plasma membrane receptor (TC II-R), a heavily glycosylated protein with a monomeric molecular mass of 62 kDa, are essential components of plasma cobalamin (Cbl; vitamin B12) transport to all cells. Evidence from studies over the past 10 years has provided some important information on their structure, regulation of expression, and function. Some of the specific findings include (a) identification of the structural relationship of the ligand TC II with other members of the Cbl-binding family of proteins, intrinsic factor (IF) and haptocorrin (HC), (b) regulation of TC II gene expression, (c) molecular basis for human TC II deficiency in patients with a lack of plasma TC II, (d) membrane expression, interactions, and dimerization of TC II-R, and (e) targeting and function of TC II-R in polarized epithelial cells. It is hoped that some of the recent findings presented in this review will provide new insights into the structure and function of these two fascinating proteins and stimulate future research in this area.

Topics: Amino Acid Sequence; Animals; Gene Expression Regulation; Humans; Intrinsic Factor; Molecular Sequence Data; Rats; Receptors, Cell Surface; Sequence Alignment; Sequence Homology, Amino Acid; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

At one time, the diagnosis of a deficiency of vitamin B12 or folate was considered to be relatively straightforward. As knowledge has accumulated, the limitations of such tests as serum vitamin level measurements and the Schilling test have become apparent. With the development of newer tests, atypical and subclinical deficiency states have been recognized. In this review, available tests used in the diagnosis of vitamin B12 and folate deficiency are discussed, and a rational approach to the diagnosis of these deficiency states is presented.

Topics: Antibodies; Clinical Laboratory Techniques; Clinical Trials as Topic; Decision Trees; Diagnosis, Differential; Erythrocytes; Folic Acid Deficiency; Hematologic Diseases; Homocysteine; Humans; Intrinsic Factor; Methylmalonic Acid; Nervous System Diseases; Parietal Cells, Gastric; Primary Health Care; Schilling Test; Vitamin B 12; Vitamin B 12 Deficiency

Recent studies have isolated and characterized human gastric intrinsic factor (IF) and transcobalamin II (TC II) genes, whose products mediate the import of cobalamin (Cbl; Vitamin B-12) across cellular plasma membranes. Analyses of cDNA and genomic clones of IF and TC II have provided some important insights into their sites of expression, structure and function. IF and TC II genes contain the same number, size and position of exons, and four of their eight intron-exon boundaries are identical. In addition, they share high homology in certain regions that are localized to different exons, indicating that IF and TC II may have evolved from a common ancestral gene. Both IF and TC II mediate transmembrane transport of Cbl via their respective receptors that function as oligomers in the plasma membrane. IF-mediated import of Cbl is limited to the apical membranes of epithelial cells; it occurs via a multipurpose receptor recently termed "cubilin," and the imported Cbl is usually exported out of these cells bound to endogenous TC II. On the other hand, TC II-mediated Cbl import occurs in all cells, including epithelial cells via a specific receptor, and the Cbl imported is usually retained, converted to its coenzyme forms, methyl-Cbl and 5'-deoxyadenosyl-Cbl, and utilized.

Topics: Animals; Cell Membrane; DNA, Complementary; Epithelium; Humans; Intrinsic Factor; Mutation; Receptors, Cell Surface; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

The disease is characterised by cobalamin (Cbl) deficiency in children 0-5 years old, causing failure to thrive, infections, megaloblastic anaemia, neuropathy, and mild general malabsorption; slight proteinuria is common. Cbl injections produce remission, but Cbl malabsorption and proteinuria persist. About 250 cases have been reported. Dogs also have it. The heredity is autosomal and recessive. The physiological and pathological absorption mechanisms are described: Cbl liberated from food by digestion is first bound to haptocorrin, but in the intestine it is transferred to intrinsic factor. In the ileum the complex attaches to a receptor on the enterocytes; this requires neutral pH and Ca2+. The receptor is a membrane-bound glycoprotein consisting of multiple subunits. The receptor-ligand complex is endocytosed and degraded in lysosomes, and the vitamin is transferred to transcobalamin which carries it to tissues. The same receptor is strongly expressed in the kidneys, but urine also contains its activity which can be assayed for diagnosis. The basic lesion is an error in the ileal receptor. In the affected dogs the synthesised receptor is retained intracellularly. Urine and ileal biopsies from human cases contained little receptor but it had conserved affinity for the ligand. Recently examined Arab patients did not excrete reduced amounts of the receptor. Apparently, the disease has subsets, such as different structural errors in the receptor and possibly faulty transport inside the enterocyte. The cause of the proteinuria is unknown but kidney damage due to severe Cbl deficiency and an error in a multiligand renal receptor are among the possibilities.

Topics: Animals; Child, Preschool; Dogs; Genes, Recessive; Humans; Infant; Infant, Newborn; Intrinsic Factor; Malabsorption Syndromes; Proteinuria; Receptors, Cell Surface; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Animals; DNA; Hematopoiesis; Humans; Intestinal Absorption; Intrinsic Factor; Receptors, Cell Surface; Tetrahydrofolates; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Deficiency Diseases; Gastrectomy; Humans; Ileal Diseases; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Nutrition Disorders; Vitamin B 12; Vitamin B 12 Deficiency

Intrinsic factor is produced by the gastric parietal cell. Its secretion is stimulated via all pathways known to stimulate gastric acid secretion: histamine, gastrin, and acetylcholine. There is, however, a different mode of secretion for both substances: atropine, vagotomy, and H2 receptor antagonists inhibit both intrinsic factor and acid secretion, but secretin and the hydrogen-potassium ATPase antagonist omeprazole have no effect on intrinsic factor while substantially reducing acid secretion. Cobalamin in food is bound to animal protein. Cobalamin deficiency due to inadequate dietary intake is rarely seen in extreme vegetarians (vegans). In the stomach cobalamin is liberated from its protein binding by peptic digestion and bound to R-proteins. Hypochlorhydria or achlorhydria, whether medically induced or not, may impair cobalamin uptake. The cobalamin-R-protein complex is split by pancreatic enzymes in the duodenum, where cobalamin is bound to intrinsic factor. Pancreatic insufficiency may lead to cobalamin deficiency. Lack of intrinsic factor is the commonest cause of cobalamin deficiency; very rarely, aberrant forms of intrinsic factor are produced, but the clinical syndrome is similar. Gram-negative anaerobe bacteria bind the cobalamin-intrinsic factor complex, and bacterial overgrowth of the small intestine diminishes cobalamin resorption. Parasitic infections with fish tape-worm and Giardia lamblia are also associated with cobalamin malabsorption. The cobalamin-intrinsic factor complex binds to the ileal receptors in the terminal ileum. Cobalamin absorption may be impaired after resection or by diseases affecting more than 50 cm of the terminal ileum, such as Crohn's disease, coeliac disease, tuberculosis, lymphoma or radiation. There is clearly a wide diversity in the aetiology of cobalamin deficiency, which requires a versatile diagnostic approach.

Topics: Humans; Intestinal Absorption; Intrinsic Factor; Vitamin B 12; Vitamin B 12 Deficiency

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

Recent evidence suggests that vitamin B12 deficiency in the elderly is more than classic pernicious anemia. Instead, it is a continuum from negative B12 balance to frank deficiency, which can be detected by low serum B12 levels long before changes occur in hemoglobin levels. Current findings in the literature suggest that subtle B12 deficiency is indeed clinically significant. Treatment may prevent significant neurologic and/or hematologic disease.

Topics: Aged; Aged, 80 and over; Drug Administration Schedule; Humans; Intrinsic Factor; Schilling Test; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Animals; Asialoglycoprotein Receptor; Digestive System; Humans; Intestinal Mucosa; Intrinsic Factor; Liver; Receptors, Cell Surface; Receptors, Immunologic; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

This monograph on the clinical chemistry of vitamin B12 reviews the literature on daily requirements, methods for measurement, the effects of drugs on vitamin B12 metabolism absorption, pregnancy, clinical conditions associated with vitamin B12 deficiency, errors of metabolism, and reactions to vitamin therapy. Although only very small quantities of vitamin B12 are required to satisfy the daily requirement, a sufficient supply is stored in the liver to meet normal requirements for at least a 3-year period. A number of drugs are known to affect the absorption of vitamin B12, including neomycin, potassium chloride, p-aminosalicylic acid, and colchicine. Significantly reduced serum concentrations of vitamin B12 have been noted in users of oral contraceptives (OCs), although concentrations still remain within the limits of normal. It appears that the vitamin B12 level in OC users reestablishes itself at a different and somewhat lower level. Vitamin B12 binding protein appears to remain unchanged. A vitamin B12 deficiency is unusual in pregnant women who consume a normal, varied diet. On the other hand, lactating women whose diets are low in animal protein and dairy products may have problems providing enough vitamin B12 to meet their own and their infant's needs; supplementary oral vitamins should be considered.

Topics: Absorption; Adult; Alcoholism; Anemia, Pernicious; Ascorbic Acid; Autoantibodies; Biguanides; Biological Transport; Chemical Phenomena; Chemistry; Chlorpromazine; Contraceptives, Oral; Diet; Female; Gastrectomy; Gastritis; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Metabolism, Inborn Errors; Middle Aged; Neoplasms; Nervous System Diseases; Nitrous Oxide; Nutritional Requirements; Pancreatic Diseases; Parasitic Diseases; Pregnancy; Pregnancy Complications; Transcobalamins; 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: Absorption; Gastric Mucosa; Humans; Ileum; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Biological Transport, Active; Carrier Proteins; Cell Division; Humans; Intestinal Absorption; Intrinsic Factor; Nervous System; Pancreas; Receptors, Drug; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Diagnosis, Differential; Folic Acid; Folic Acid Deficiency; Humans; Hydrolysis; Intestinal Absorption; Intestinal Mucosa; Intrinsic Factor; Malabsorption Syndromes; Pancreas; Pteroylpolyglutamic Acids; Sprue, Tropical; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Animals; Calcium; Chronic Disease; Humans; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Pancreatectomy; Pancreatic Diseases; Pancreatic Juice; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Absorption; Aged; Anemia; Anemia, Pernicious; Chemical Phenomena; Chemistry; Food Analysis; Gastrointestinal Diseases; Humans; Intrinsic Factor; Malabsorption Syndromes; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Absorption; Aged; Anemia, Pernicious; Animals; Biological Transport; Chemical Phenomena; Chemistry; Child; Diphyllobothriasis; Food Analysis; Humans; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Nutritional Requirements; Stomach; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency; Zollinger-Ellison Syndrome

Topics: Adrenal Cortex Hormones; Anemia, Pernicious; Animals; Antigen-Antibody Complex; Antigens; Autoantibodies; Autoimmune Diseases; Chronic Disease; Dogs; Female; Gastric Mucosa; Gastrins; Gastritis; Guinea Pigs; Haplorhini; Humans; Immunity, Cellular; Intrinsic Factor; Male; Rabbits; Rats; 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; Anemia; Animals; Biological Transport; Blind Loop Syndrome; Calcium; Gastric Mucosa; Gastritis; Guinea Pigs; Humans; Hydrogen-Ion Concentration; Ileum; Intestinal Absorption; Intestinal Diseases, Parasitic; Intestinal Mucosa; Intrinsic Factor; Male; Pancreatic Diseases; Radiation Effects; Rats; Thalassemia; Trypsin; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Alcoholism; Anemia, Hypochromic; Anemia, Macrocytic; Anemia, Pernicious; Diagnosis, Differential; Folic Acid; Folic Acid Antagonists; Folic Acid Deficiency; Humans; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Pyrimidine Nucleotides; Thymine Nucleotides; Uracil Nucleotides; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Blind Loop Syndrome; Humans; Intestinal Mucosa; Intestine, Small; Intrinsic Factor; Protein Binding; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Age Factors; Diet; Female; Folic Acid; Folic Acid Deficiency; Gastrointestinal Diseases; Humans; Infant; Intrinsic Factor; Malabsorption Syndromes; Metabolic Diseases; Metabolism, Inborn Errors; Nutrition Disorders; Nutritional Physiological Phenomena; Nutritional Requirements; Pregnancy; Time Factors; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adolescent; Anemia, Pernicious; Animals; Child; Child Nutritional Physiological Phenomena; Female; Humans; Ileum; Infant; Intrinsic Factor; Malabsorption Syndromes; Male; Schilling Test; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Achlorhydria; Anemia, Pernicious; Animals; Binding Sites; Biological Transport; Blind Loop Syndrome; Cestode Infections; Folic Acid Deficiency; Humans; Intestinal Absorption; Intestine, Small; Intrinsic Factor; Liver; Malabsorption Syndromes; Pancreas; Postgastrectomy Syndromes; Protein Binding; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Bile; Binding Sites; Feces; Folic Acid; Folic Acid Deficiency; Humans; Intestinal Absorption; Intrinsic Factor; Protein Binding; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Animals; Body Weight; Folic Acid; Humans; Ileum; Intestinal Absorption; Intrinsic Factor; Liver; Receptors, Drug; Schilling Test; Sprue, Tropical; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Administration, Oral; Anemia, Pernicious; Cobalt Isotopes; Gastric Juice; Half-Life; Humans; Ileum; Intestinal Absorption; Intrinsic Factor; Liver; Malabsorption Syndromes; Pancreas; Schilling Test; Stomach; Vitamin B 12; Vitamin B 12 Deficiency; Whole-Body Counting

Topics: Anemia, Macrocytic; Anemia, Pernicious; Coenzymes; Humans; Intestinal Absorption; Intrinsic Factor; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Diagnosis, Differential; Humans; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Gastric Mucosa; Humans; Intestinal Absorption; Intestines; Intrinsic Factor; Malabsorption Syndromes; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Hypochromic; Anemia, Pernicious; Animals; Burns, Chemical; Celiac Disease; Diagnosis, Differential; Gastric Juice; Gastritis; Humans; In Vitro Techniques; Intrinsic Factor; Peptic Ulcer; Stomach Neoplasms; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; History, 19th Century; History, 20th Century; Humans; Intrinsic Factor; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Anemia, Pernicious; Child; Child, Preschool; Diphyllobothriasis; Female; Folic Acid Deficiency; Humans; Infant; Infant Nutrition Disorders; Infant, Newborn; Intrinsic Factor; Kwashiorkor; Malabsorption Syndromes; Male; Proteinuria; Thiamine; Transferases; Vitamin B 12 Deficiency

Topics: Adolescent; Anemia, Pernicious; Autoantibodies; Child; Chronic Disease; Female; Gastric Mucosa; Humans; Hydrogen-Ion Concentration; Ileum; Infant; Intestinal Mucosa; Intrinsic Factor; Malabsorption Syndromes; Male; Pancreatic Diseases; Pregnancy; Vitamin B 12 Deficiency

Topics: Anemia; Anemia, Hypochromic; Anemia, Macrocytic; Female; Folic Acid Deficiency; Gastrectomy; Humans; Intestinal Absorption; Intrinsic Factor; Iron; Vitamin B 12 Deficiency

Topics: Age Factors; Anemia, Pernicious; Antibodies; Atrophy; Bethanechol Compounds; Carbachol; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Histamine; Humans; Insulin; Intrinsic Factor; Methacholine Compounds; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Animals; Ascorbic Acid; Biological Transport; Cats; Dogs; Folic Acid; Humans; Intestinal Absorption; Intrinsic Factor; Rats; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex; Vitamins

Topics: Anemia, Pernicious; Clinical Trials as Topic; Humans; Intrinsic Factor; Malabsorption Syndromes; Postgastrectomy Syndromes; Schilling Test; Vitamin B 12; Vitamin B 12 Deficiency

Crude preparations of hog gastric intrinsic factor or their own previously collected gastric juices administered with labeled vitamin B12 did not enhance vitamin B12 absorption in patients with vitamin B12 malabsorption secondary to pancreatic insufficiency. However, when these sources of gastric intrinsic factor were incubated with three times crystallized preparations of insolubilized bovine trypsin or chymotrypsin, the proteolytic enzymes were removed by centrifugation, and the preparations of gastric intrinsic factor were readministered to these patients, the absorption of vitamin B12 was markedly enhanced. Studies of hog gastric intrinsic factor before and after exposure to proteolytic enzymes failed to show any difference on Sephadex chromatography or polyacrylamide gel electrophoresis or on its affinity for vitamin B12 or the ileal receptor in guinea pigs. These investigations demonstrate that: (1) gastric intrinsic factor as secreted by subjects with pancreatic insufficiency or obtained from hog pyloric mucosal extracts is ineffective in promoting vitamin B12 absorption in patients with pancreatic insufficiency, (2) incubation of crude preparations of gastric intrinsic factor with insolubilized pancreatic proteases modified these preparations of gastric intrinsic factor in an as yet undefined manner, allowing them to enhance vitamin B12 absorption, and (3) in vitro studies using gut sacs or brush border preparations do not reflect the abnormality in vitamin B12 absorption associated with pancreatic dysfunction.

Topics: Anemia, Pernicious; Animals; Chymotrypsin; Clinical Trials as Topic; Female; Gastric Juice; Guinea Pigs; Humans; Intestinal Absorption; Intrinsic Factor; Pancreatic Diseases; Pancreatic Juice; Peptide Hydrolases; Swine; Trypsin; Vitamin B 12 Deficiency

Topics: Aged; Anemia, Pernicious; Clinical Trials as Topic; Humans; Intrinsic Factor; Malabsorption Syndromes; Middle Aged; Radioisotopes; Schilling Test; Spectrometry, Gamma; Time Factors; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Animals; Biological Assay; Cathartics; Cobalt Isotopes; Colchicine; Feces; Female; Gastric Juice; Gastric Mucosa; Gastrointestinal Motility; Guinea Pigs; Humans; Ileum; Immunoassay; In Vitro Techniques; Intestinal Absorption; Intestinal Mucosa; Intrinsic Factor; Male; Schilling Test; Vitamin B 12; Vitamin B 12 Deficiency

Vitamin B12, or cobalamin, is a nutrient that is vital for metabolic function. Absorption of ingested B12 is dependent on intrinsic factor, which is secreted by parietal cells within the stomach. Pernicious anemia is caused by an intrinsic factor deficiency or autoantibodies against intrinsic factor. The presence of parietal cell antibodies can destroy parietal cells, which can also lead to a deficiency in intrinsic factor. Both lead to megaloblastic anemia caused by vitamin B12 deficiency. The typical presentation of pernicious anemia includes fatigue, pale appearance, tingling sensation, depression, alterations to vision and smell, urinary incontinence, psychotic episodes, and weakness. The most effective treatment for pernicious anemia is intramuscular B12.. A 27-year-old woman with a history of vitiligo presented to the emergency department (ED) with bilateral lower extremity weakness, clumsiness, numbness, and tingling. Physical examination revealed ataxia, no sensation below her umbilicus, decreased strength, and hyperreflexia in both lower extremities. Complete blood count in the ED revealed low hemoglobin and hematocrit and elevated mean corpuscular volume, concerning for pernicious anemia. Further laboratory testing upon inpatient admission revealed a low vitamin B12 level and parietal cell antibodies in the blood. The patient's pernicious anemia was treated with intramuscular vitamin B12 injections, which led to near complete resolution of her symptoms. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Early suspicion and detection of pernicious anemia in the ED can prevent serious and permanent hematologic and neurologic damage and the development of other autoimmune disorders.

Topics: Adult; Anemia, Pernicious; Ataxia; Autoantibodies; Female; Humans; Intrinsic Factor; Paresthesia; Vitamin B 12; Vitamin B 12 Deficiency

Background Vitamin B12 deficiency is common worldwide and is also linked to several diseases including autoimmune atrophic gastritis (AAG). The presence of anti-parietal cell antibodies (APCA) and/or intrinsic factor blocking antibodies (IFBA) is indicative of AAG that may develop into pernicious anemia. Both conditions are known to be associated with an increased risk of gastric carcinoma. The aim of this study was to estimate the frequency of individuals positive for APCA and IFBA antibodies in primary care patients with severe vitamin B12 deficiency. Methods An observational study was designed and 5468 consecutive patients from primary care with a request for vitamin B12 status were included and add-on testing for APCA and IFBA that were automatically registered if severe vitamin B12 deficiency was identified (<73.8 pmol/L). For patients included in the intervention, study demographic data, mean corpuscular volume (MCV) and hemoglobin values were collected. Results Seventy-seven patients with severe vitamin B12 deficiency were identified and out of these 44 (57%) presented with antibodies to APCA and 11 (14%) to IFBA, 25 (32.5%) had anemia, and 25 (32.5%) had macrocytosis. The majority of APCA and/or IFBA positive patients were found in the age group >70 years. Both anemia and macrocytosis were more common among APCA positive patients but the association was not statistically significant, neither was the correlation between IFBA status and anemia and/or macrocytosis. Among the patients with anemia, 10 (39%) had macrocytosis, although the rate of macrocytosis among patients with or without anemia did not differ significantly. Conclusions The automated analysis strategy of measuring antibodies to APCA and IFBA in patients with severe vitamin B12 deficiency, efficiently detected positivity in more than 60% the patients. The result point to the presence of a high rate of otherwise undetected AAG and the potential clinical utility of APCA and IFBA as markers in primary care.

Topics: Adult; Aged; Antibodies, Neutralizing; Female; Humans; Intrinsic Factor; Male; Middle Aged; Primary Health Care; Vitamin B 12 Deficiency; Young Adult

Hereditary intrinsic factor deficiency is a rare disease characterized by cobalamin deficiency with the lack of gastric intrinsic factor because of gastric intrinsic factor (GIF) mutations. Patients usually present with cobalamin deficiency without gastroscopy abnormality and intrinsic factor antibodies.. A Chinese patient presented with recurrent severe anemia since age 2 with low cobalamin level and a mild elevation of indirect bilirubin. The hemoglobin level normalized each time after intramuscular vitamin B12 injection. Gene test verified a c.776delA frame shift mutation in exon 6 combined with c.585C > A nonsense early termination mutation in exon 5 of GIF which result in the dysfunction of gastric intrinsic factor protein. The hereditary intrinsic factor deficiency in literature was further reviewed and the ancestry of different mutation sites were discussed.. A novel compound heterozygous mutation of GIF in a Chinese patient of hereditary intrinsic factor deficiency was reported. It was the first identified mutation of GIF in East-Asia and may indicate a new ancestry.

Topics: Adolescent; Anemia, Pernicious; Base Sequence; Bilirubin; China; Exons; Frameshift Mutation; Gastric Mucosa; Gene Expression; Hemoglobins; Humans; Intrinsic Factor; Male; Pedigree; Vitamin B 12; Vitamin B 12 Deficiency

This study aimed to report the case of a patient who presented with depression, cognitive impairment, ataxic gait, and urinary incontinence associated with vitamin B12 deficiency.. Serum vitamin B12 level was low in this patient, and anti-intrinsic factor antibody was positive. Neuroimaging revealed abnormal hyperintense signals in the cerebellum and dorsal and lateral columns of the spinal cord, and obstructive hydrocephalus. A biopsy of the stomach revealed chronic gastritis, intestinal metaplasia, and atrophy. After 3 months of initiating methylcobalamin therapy, significant improvement was noticed clinically, and brain magnetic resonance imaging was near to normal.. This study was novel in reporting subacute combined degeneration of the spinal cord and hydrocephalus associated with vitamin B12 deficiency in adults.

Topics: Adult; Gastritis, Atrophic; Humans; Hydrocephalus; Intrinsic Factor; Male; Subacute Combined Degeneration; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex

Topics: Anemia, Pernicious; Diagnosis, Differential; Humans; Intrinsic Factor; Magnetic Resonance Imaging; Male; Memory Disorders; Middle Aged; Muscle Weakness; Spinal Cord; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Autoantibodies; Enzyme-Linked Immunosorbent Assay; Humans; Immunoglobulin G; Intrinsic Factor; Reagent Kits, Diagnostic; Sensitivity and Specificity; Vitamin B 12 Deficiency

Topics: Adult; Autoimmune Diseases; Diagnosis, Differential; Female; HELLP Syndrome; Humans; Intrinsic Factor; Pregnancy; Vitamin B 12 Deficiency

To evaluate the presence of intrinsic factor antibody in vitamin B12 deficient patients.. Cross-sectional, observational study.. Fauji Foundation Hospital, Foundation University Medical College and Armed Forces Institute of Pathology, Rawalpindi, from January 2011 to June 2012.. A total of 120 patients of megaloblastic anaemia were selected on the basis of low serum vitamin B12 level. The intrinsic factor antibody tests were performed by ELISA method. The patients were considered positive or negative on the basis of presence or absence of intrinsic factor antibody respectively. The data was analyzed by using SPSS version 14.. Pernicious anaemia with intrinsic factor deficiency was found in 13.3% in 120 vitamin B12 deficient patients. The mean age of patients of pernicious anaemia was 41.5 years, with a male to female ratio of 1:2.5. It was relatively more common in older age (17% in age more than 60 years) as compared to other age groups.. Frequency of pernicious anaemia in megaloblastic anaemia was 13.3%. The male to female ratio was 1:2.5 and it was relatively more common in age group of more than 60 years.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Pernicious; Autoantibodies; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Intrinsic Factor; Male; Middle Aged; Pakistan; Prevalence; Sex Distribution; Vitamin B 12; Vitamin B 12 Deficiency

Both maternal and offspring-derived factors contribute to lifelong growth and bone mass accrual, although the specific role of maternal deficiencies in the growth and bone mass of offspring is poorly understood. In the present study, we have shown that vitamin B12 (B12) deficiency in a murine genetic model results in severe postweaning growth retardation and osteoporosis, and the severity and time of onset of this phenotype in the offspring depends on the maternal genotype. Using integrated physiological and metabolomic analysis, we determined that B12 deficiency in the offspring decreases liver taurine production and associates with abrogation of a growth hormone/insulin-like growth factor 1 (GH/IGF1) axis. Taurine increased GH-dependent IGF1 synthesis in the liver, which subsequently enhanced osteoblast function, and in B12-deficient offspring, oral administration of taurine rescued their growth retardation and osteoporosis phenotypes. These results identify B12 as an essential vitamin that positively regulates postweaning growth and bone formation through taurine synthesis and suggests potential therapies to increase bone mass.

Topics: Animals; Bone Density; Bone Development; Female; Growth; Growth Disorders; Growth Hormone; Insulin-Like Growth Factor I; Intrinsic Factor; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Osteoporosis; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; STAT5 Transcription Factor; Taurine; Vitamin B 12; Vitamin B 12 Deficiency

It is believed that Pernicious anaemia (PA) is more common in the West. We postulate however that in India PA is probably an important aetiological factor as a cause of Vitamin B12 deficiency in patients having neurological disease.. To investigate the aetiological factors resulting in Vitamin B12 (Vit B12) deficiency in patients with subacute combined degeneration (SACD) and other neurological manifestations.. We undertook a prospective study of 50 patients, all clinically suspected to have Vit B12 deficiency; they were investigated clinically, haematologically, biochemically and radiologically.. There was a dominance of males (41 of 50) with the majority in the age group of more than 40 years of age. There was no correlation between the socio-economic and dietary status on the one hand and the clinical manifestation on the other. Anti intrinsic factor antibodies (AIFAB) were positive in 19 of 50 patients (38%) and anti parietal cell antibodies (APCAB) were positive in 28 of 50 (56%) patients.. We conclude that Pernicious anaemia is an important cause of various neurological manifestations including SACD in the Vitamin B12 deficient population in the age group of more than 40 years, irrespective of the socio-economic and dietary status in the Indian subcontinent. It is supported by the presence of AIFAB or APCAB in this group.

Topics: Adult; Aged; Anemia, Pernicious; Autoantibodies; Cross-Sectional Studies; Diet, Vegetarian; Female; Humans; India; Intrinsic Factor; Male; Middle Aged; Nervous System Diseases; Neurologic Examination; Parietal Cells, Gastric; Risk Factors; Subacute Combined Degeneration; Vitamin B 12 Deficiency

Topics: Child, Preschool; Female; Humans; Intrinsic Factor; Mutation; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Vitamin B 12 Deficiency

Parietal cell antibody is a marker for autoimmune gastritis. With identification of gastric H/K ATPase as its molecular target, ELISAs have been introduced. We compared performance of ELISA with immunofluorescence in a retrospective and prospective sera set and correlated the results with intrinsic factor antibody. In 138 retrospective sera selected for positivity or negativity for intrinsic factor antibody, 87 reacted with gastric H/K ATPase by Euroimm ELISA but only 62 reacted by immunofluorescencence.. Similar results were obtained with Inova ELISA with 78 positives that were also positive by Euroimm ELISA. In 161 prospective sera, 29 sera tested positive by ELISA compared to 24 by immunofluorescence. ELISA positive but immunofluoresnce negative sera are bona fide positives because a representative set of 16 sera reacted with both 95kD α and 60-90kDβ subunits of gastric H/K ATPase. ELISA values rose with age regardless of whether immunofluorescence tests were positive or negative. Of 53 sera containing antibody to intrinsic factor, 46/53 (87%) reacted to gastric H/K ATPase by ELISA. Taken together, the data indicates an enhanced detection rate by ELISA over immunofluorescence and validates it as a robust diagnostic assay for parietal cell antibody. As parietal cell antibody marks asymptomatic autoimmune gastritis that may progress to end stage gastric atrophy and haematological complications, and as autoimmune gastritis is associated with autoimmune thyroiditic and type 1 diabetes mellitus, early detection of parietal cell antibody by a sensitive ELISA will enable early follow-up of at risk subjects.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Autoantibodies; Autoimmune Diseases; Enzyme-Linked Immunosorbent Assay; Erythrocytes, Abnormal; Female; Fluorescent Antibody Technique; Gastritis; H(+)-K(+)-Exchanging ATPase; Hematologic Diseases; Humans; Intrinsic Factor; Male; Middle Aged; Parietal Cells, Gastric; Retrospective Studies; Vitamin B 12 Deficiency; Young Adult

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

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

A 28 month-old boy was hospitalized with pallor and weight stagnation. He had macrocytic anaemia and pancytopenia due to cobalamin deficiency and a rare homozygous mutation in the intrinsic factor gene. His sister showed similar symptoms at the age of 15 months. The heterozygous father had no symptoms, but did have a low cobalamin level. Gastroscopy with biopsies showed no pathology. All were given monthly cyanocobalamin injections which, however, caused leg cramps. Replacement with monthly hydroxocobalamin was successful.

Topics: Child, Preschool; Female; Growth; Homozygote; Humans; Hydroxocobalamin; Infant; Intrinsic Factor; Male; Mutation; Vitamin B 12 Deficiency; Vitamin B Complex

To study the association between Helicobacter pylori (H. pylori) infection and autoimmune type atrophic gastritis.. Twenty-three patients with different grades of atrophic gastritis were analysed using enzyme immunoassay-based serology, immunoblot-based serology, and histology to reveal a past or a present H. pylori infection. In addition, serum markers for gastric atrophy (pepsinogen I, pepsinogen I/II and gastrin) and autoimmunity [parietal cell antibodies (PCA), and intrinsic factor (IF), antibodies] were determined.. Of the 14 patients with severe gastric atrophy, as demonstrated by histology and serum markers, and no evidence for an ongoing H. pylori infection, eight showed H. pylori antibodies by immunoblotting. All eight had elevated PCA and 4/8 also had IF antibodies. Of the six immunoblot-negative patients with severe corpus atrophy, PCA and IF antibodies were detected in four. Among the patients with low to moderate grade atrophic gastritis (all except one with an ongoing H. pylori infection), serum markers for gastric atrophy and autoimmunity were seldom detected. However, one H. pylori negative patient with mild atrophic gastritis had PCA and IF antibodies suggestive of a pre-atrophic autoimmune gastritis.. Signs of H. pylori infection in autoimmune gastritis, and positive autoimmune serum markers in H. pylori gastritis suggest an etiological role for H. pylori in autoimmune gastritis.

Topics: Aged; Autoantibodies; Autoimmune Diseases; Biomarkers; Female; Gastrins; Gastritis, Atrophic; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Immunoblotting; Immunoenzyme Techniques; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Parietal Cells, Gastric; Pepsinogen A; Pepsinogen C; Risk Factors; Severity of Illness Index; Vitamin B 12 Deficiency

Topics: Adult; Anemia, Pernicious; Anemia, Sickle Cell; Autoantibodies; Depression; Female; Folic Acid; Gastrins; Hemoglobin SC Disease; Humans; Hydroxyurea; Hyperhomocysteinemia; Intrinsic Factor; Iron Overload; Male; Methylmalonic Acid; Pneumonia; Transcobalamins; Transfusion Reaction; Treatment Refusal; Vitamin B 12; Vitamin B 12 Deficiency; Young Adult

Topics: Adolescent; Humans; Intrinsic Factor; Male; Mutation; Vitamin B 12 Deficiency

Leukoencephalopathy and autonomic dysfunction have been described in individuals with very low serum B(12) levels (<200 pg/ml), in addition to psychiatric changes, neuropathy, dementia and subacute combined degeneration. Elevated homocysteine and methylmalonic acid levels are considered more sensitive and specific for evaluating truly functional B(12) deficiency. A previously healthy 62-year-old woman developed depression and cognitive deficits with autonomic dysfunction that progressed over the course of 5 years. The patient had progressive, severe leukoencephalopathy on multiple MRI scans over 5 years. Serum B(12) levels ranged from 267 to 447 pg/ml. Homocysteine and methylmalonic acid levels were normal. Testing for antibody to intrinsic factor was positive, consistent with pernicious anaemia. After treatment with intramuscular B(12) injections (1000 μg daily for 1 week, weekly for 6 weeks, then monthly), she made a remarkable clinical recovery but remained amnesic for major events of the last 5 years. Repeat MRI showed partial resolution of white matter changes. Serum B(12), homocysteine and methylmalonic acid levels are unreliable predictors of B(12)-responsive neurologic disorders, and should be thoroughly investigated and presumptively treated in patients with unexplained leukoencephalopathy because even long-standing deficits may be reversible.

Topics: Autoantibodies; Autonomic Nervous System Diseases; Brain; Cognition Disorders; Depressive Disorder; Drug Therapy, Combination; Female; Homocysteine; Humans; Intrinsic Factor; Leukoencephalopathies; Magnetic Resonance Imaging; Mental Status Schedule; Methylmalonic Acid; Middle Aged; Neurologic Examination; Psychometrics; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin D

Topics: Black People; Child; Female; Founder Effect; Humans; Intrinsic Factor; Male; Mutation; Pedigree; Vitamin B 12 Deficiency

Atrophic body gastritis (ABG) is an autoimmune condition eventually manifesting itself as pernicious anemia (PA). Parietal cell autoantibodies (PCAs) and intrinsic factor autoantibodies (IFAs) are considered characteristics of these conditions. Recent studies on IFA and PCA frequency with respect to cobalamin deficiency in biopsy-proven ABG patients are lacking. We addressed this issue using new enzyme-linked immunosorbent assay (ELISA)-based assays.. Sera from 165 patients with histologically diagnosed ABG and 113 controls were tested for IFA and PCA using ELISA. A total of 81 ABG patients had cobalamin deficiency and macrocytic anemia (Group 1-PA), 36 had cobalamin deficiency without macrocytic anemia (Group 2), and 48 had normal cobalamin levels (Group 3).. IFAs were detected in 44/165 ABG patients (27% sensitivity) and in 0/113 controls (100% specificity). PCAs were detected in 134 ABG patients (81% sensitivity) and in 11 controls (90% specificity). In Group 1, IFAs showed 37% sensitivity and 100% specificity, whereas PCAs showed 81% sensitivity and 90% specificity. Combining IFA and PCA testing increased the sensitivity to 61% in all ABG patients and to 73% in Group 1, while maintaining 100% specificity.. IFAs are 100% specific for biopsy-proven ABG and occurred in 27% of patients. PCAs occurred in 81% of ABG patients and in 10% of controls. Combining IFA and PCA testing significantly increases their diagnostic performance for ABG and PA, yielding a 73% sensitivity for PA. The non-invasive combined PCA and IFA assessment may be useful in selecting patients at risk for autoimmune gastritis to be confirmed by gastroscopic-histologic examination.

Topics: Adult; Autoantibodies; Female; Gastritis, Atrophic; Humans; Intrinsic Factor; Male; Middle Aged; Parietal Cells, Gastric; Vitamin B 12 Deficiency

The objective of the study is to evaluate the concordance of four assays for antibodies against intrinsic factor (IF-Ab). Sixty-two sera were tested with one competitive automated and three manual noncompetitive assays. Thirty-five percent patients had discordant results with at least one of the four assays. However, any method uncovered patients with proven Biermer's disease missed by the others assays. The observed discordance partly explains the poor sensitivity of IF-Ab in studies using a single assay.

Topics: Anemia, Pernicious; Autoantibodies; Diagnosis, Differential; Humans; Intrinsic Factor; Predictive Value of Tests; Reproducibility of Results; Vitamin B 12 Deficiency

Homocysteine is a risk factor for the development of thromboembolic disorders and vascular diseases. Furthermore, complications during pregnancy have been ascribed to hyperhomocysteinemia. We report on a pregnant woman being substituted by high doses folic acid for hyperhomocysteinemia. Thereby, the underlying pernicious anemia was masked. After birth, the neonate was exclusively breastfed. At the age of 5 months, the infant had to be admitted to hospital due to severe vitamin B(12)-deficiency. Using parenteral vitamin B(12) substitution, homocystein levels of the mother normalized and the infant throve and prospered again.

Topics: Abortion, Habitual; Adult; Anemia, Pernicious; Autoimmune Diseases; Breast Feeding; Diagnosis, Differential; Failure to Thrive; Female; Folic Acid; Gastritis, Atrophic; Homocysteine; Humans; Infant; Intrinsic Factor; Methylmalonic Acid; Parietal Cells, Gastric; Pregnancy; Thromboembolism; Vitamin B 12 Deficiency

Topics: Adult; Amino Acid Substitution; Anemia, Pernicious; Gastric Mucosa; Genetic Predisposition to Disease; Genotype; Humans; Intestinal Absorption; Intrinsic Factor; Mutation, Missense; Point Mutation; Risk; Vitamin B 12; Vitamin B 12 Deficiency

Helicobacter pylori gastritis may lead to impairment of the production of pepsinogen and acid, which are essential to cobalamin absorption. In turn, cobalamin deficiency leads to hyperhomocysteinaemia, a risk factor for cardio and cerebrovascular diseases.. To evaluate the effect of H pylori eradication on plasma homocysteine levels in elderly patients.. Sixty-two H pylori-positive elderly patients with cobalamin deficiency were prospectively studied.. Homocysteine and cobalamin concentrations were determined before, 6 and 12 months after H pylori eradication.. Corpus atrophy was observed in a few patients; otherwise, in most of them, the degree of corpus gastritis was moderate to severe. The initial homocysteine mean (SD) levels decreased from 41.0 (27.1) to 21.6 (10.1) micromol/l at the 6 month follow-up (p<0.001) and to 13.1 (3.8) micromol/l 12 months after H pylori eradication (p<0.001). Conversely, initial cobalamin mean levels increased from 145.5 (48.7) pmol/l to 209.8 (87.1) pmol/l and to 271.2 (140.8) pmol/l, 6 and 12 months after treatment, respectively (p<0.001 for both). Although the erythrocyte mean corpuscular volume was within reference intervals, it decreased significantly 6 (p = 0.002) and 12 (p<0.001) months after treatment.. The results of the current study demonstrated that the eradication of H pylori in elderly patients with cobalamin deficiency is followed by increasing of cobalamin and decreasing of homocysteine blood levels.

Topics: Aged; Aged, 80 and over; Autoantibodies; Female; Follow-Up Studies; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Homocysteine; Humans; Intrinsic Factor; Male; Middle Aged; Parietal Cells, Gastric; Pepsinogen A; Prospective Studies; Vitamin B 12 Deficiency

Researchers have developed murine lymphopenic, non-lymphopenic, transgenic, spontaneous and infectious agent based models to induce an experimental autoimmune gastritis (EAG) for the study of human organ-specific autoimmune disease. These models result in a chronic inflammatory mononuclear cell infiltrate in the gastric mucosa, destruction of parietal and zymogenic cells with autoantibodies reactive to the gastric parietal cells and the gastric H+/K+ ATPase (ATP4), arguably hallmarks of a human autoimmune gastritis (AIG). In the case of AIG, it is well documented that, in addition to parietal cell antibodies being detected in up to 90% of patients, up to 70% have intrinsic factor antibodies with the later antibodies considered highly specific to patients with pernicious anemia. This is the first report specifically investigating the occurrence of intrinsic factor antibodies, cobalamin deficiency and pernicious anemia in EAG models. We conclude, in contrast to AIG, that, in the three EAG models examined, intrinsic factor is not selected as a critical autoantigen.

Topics: Anemia, Pernicious; Animals; Autoantibodies; Autoantigens; Autoimmune Diseases; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Female; Gastritis; H(+)-K(+)-Exchanging ATPase; Immunoblotting; Intrinsic Factor; Male; Mice; Mice, Inbred BALB C; Mice, Transgenic; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Brain; Diagnosis, Differential; Gastric Mucosa; Humans; Injections, Intramuscular; Intrinsic Factor; Liver; Patient Education as Topic; Schilling Test; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Gastric Acid; Humans; Intrinsic Factor; Middle Aged; Pepsin A; Vitamin B 12; Vitamin B 12 Deficiency

We report on the use of recombinant human intrinsic factor (rhIF) in a new vitamin B12 absorption test. Holotranscobalamin (holoTC) was measured before and 24 hours after intake of three 9-mg doses of vitamin B12 (B12) and again 24 hours after intake of the same dose of B12 together with rhIF (rhIF-B12). Nine patients with evident vitamin B12 deficiency had a significantly higher increase in holoTC after intake of rhIF-B12 than after intake of B12. Twenty-eight patients with suspected vitamin B12 deficiency showed no additional increase in holoTC after intake of rhIF-B12. We conclude that rhIF promotes B12 absorption among patients with evident vitamin B12 deficiency.

Topics: Biological Transport; Humans; Intestinal Absorption; Intrinsic Factor; Recombinant Proteins; Vitamin B 12; Vitamin B 12 Deficiency

Vitamin B12 deficiency due to malnutrition or malabsorption may lead to pernicious anemia and neurological disorders. Although randomized prospective studies have shown that pernicious anemia can be safely treated with oral vitamin B12 even in the absence of intrinsic factor, it is still common practice to treat patients with neurological symptoms with intramuscular cyancobalamin injections. We report the successful oral treatment of subacute combined degeneration of the spinal cord in a 24-year-old woman closely monitored clinically with MRI and plasma levels of vitamin B12, homocysteine, and methylmalonic acid. We suggest monitored oral substitution therapy as first-line therapy for neurological disorders related to vitamin B12 deficiency.

Topics: Administration, Oral; Adult; Anemia, Pernicious; Autoantibodies; Dose-Response Relationship, Drug; Female; Folic Acid; Homocysteine; Humans; Intrinsic Factor; Magnetic Resonance Imaging; Methylmalonic Acid; Neurologic Examination; Spinal Cord; Spinal Cord Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Aged; Humans; Intestinal Absorption; Intrinsic Factor; Memory Disorders; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Autoanalysis; Autoantibodies; Autoimmune Diseases; Female; Humans; Immunoassay; Intrinsic Factor; Luminescent Measurements; Male; Reference Values; Serum; Vitamin B 12; Vitamin B 12 Deficiency

Hereditary juvenile megaloblastic anemia due to vitamin B12 (cobalamin) deficiency is caused by intestinal malabsorption of cobalamin. In Imerslund-Grasbeck syndrome (IGS), cobalamin absorption is completely abolished and not corrected by the administration of intrinsic factor (IF); if untreated, the disease is fatal. Biallelic mutations either in the cubilin (CUBN) or amnionless (AMN) gene cause IGS. In a series of families clinically diagnosed with likely IGS, at least six displayed no evidence of mutations in CUBN or AMN. A genome-wide search for linkage followed by mutational analysis of candidate genes was performed in five of these families. A region in chromosome 11 showed evidence of linkage in four families. The gastric IF (GIF) gene located in this region harbored homozygous nonsense and missense mutations in these four families and in three additional families. The disease in these cases therefore should be classified as hereditary IF deficiency. Clinically, these patients resembled those with typical IGS; radiocobalamin absorption tests had been inconclusive regarding the nature of the defect. In the diagnosis of juvenile cobalamin deficiency, mutational analysis of the CUBN, AMN, and GIF genes provides a molecular characterization of the underlying defect and may be the diagnostic method of choice.

Topics: Chromosome Mapping; Chromosomes, Human, Pair 11; Female; Humans; Intrinsic Factor; Male; Mutation; Pedigree; 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

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

The common but incompletely understood entity of malabsorption of food bound cobalamin is generally presumed to arise from gastritis and/or achlorhydria.. To conduct a systematic comparative examination of gastric histology and function.. Nineteen volunteers, either healthy or with low cobalamin levels, were prospectively studied without prior knowledge of their absorption or gastric status.. All subjects underwent prospective assessment of food cobalamin absorption by the egg yolk cobalamin absorption test, endoscopy, histological grading of biopsies from six gastric sites, measurement of gastric secretory function, assay for serum gastrin and antiparietal cell antibodies, and direct tests for Helicobacter pylori infection.. The six subjects with severe malabsorption (group I) had worse histological scores overall and lower acid and pepsin secretion than the eight subjects with normal absorption (group III) or the five subjects with mild malabsorption (group II). However, histological findings, and acid and pepsin secretion overlapped considerably between individual subjects in group I and group III. Two distinct subgroups of three subjects each emerged within group I. One subgroup (IA) had severe gastric atrophy and achlorhydria. The other subgroup (IB) had little atrophy and only mild hypochlorhydria; the gastric findings were indistinguishable from those in many subjects with normal absorption. Absorption improved in the two subjects in subgroup IB and in one subject in group II who received antibiotics, along with evidence of clearing of H pylori. None of the subjects in group IA responded to antibiotics.. Food cobalamin malabsorption arises in at least two different gastric settings, one of which involves neither gastric atrophy nor achlorhydria. Malabsorption can respond to antibiotics, but only in some patients. Food cobalamin malabsorption is not always synonymous with atrophic gastritis and achlorhydria, and hypochlorhydria does not always guarantee food cobalamin malabsorption.

Topics: Achlorhydria; Adult; Aged; Aged, 80 and over; Biopsy; Case-Control Studies; Female; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Gastroscopy; Helicobacter pylori; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Parietal Cells, Gastric; Prospective Studies; Schilling Test; Vitamin B 12 Deficiency

Although it is recognized that glossitis is a classical sign of pernicious anemia, occurring in the evolution of this disease, it is unfrequent for this sign to reveal this affection. We report two cases where diagnosis was evacuated on the presence of glossitis and macrocytosis despite absence of anemia. Confirmation was done by low serum cobalamin level, gastritis atrophy and presence of intrinsic factor antibody. We emphasize that increased clinical suspicion may lead to early diagnosis even if anemia is lacking.

Topics: Aged; Anemia, Pernicious; Autoimmune Diseases; Erythrocyte Indices; Female; Glossitis; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Vitamin B 12 Deficiency

Topics: Aged; Aged, 80 and over; Autoantibodies; Autoimmune Diseases; Female; HLA-DR3 Antigen; HLA-DR4 Antigen; Humans; Hypothyroidism; Intrinsic Factor; Parietal Cells, Gastric; Sjogren's Syndrome; Syndrome; Thyroiditis, Autoimmune; Vitamin B 12 Deficiency; Xerostomia

A Johns Hopkins University study reveals that HIV-infected men with abnormally low B vitamin blood levels progressed to AIDS twice as fast as those with normal levels. Low levels of B12 have also been found in persons with Chronic Fatigue Immune Dysfunction Syndrome (CFID). Since both ailments have a common virus in HHV-6A, the virus is suspected, although unproven, of causing the inability of the intestines to absorb B12 by affecting intrinsic factor levels.

Topics: Acquired Immunodeficiency Syndrome; Cognition Disorders; Fatigue Syndrome, Chronic; Herpesvirus 6, Human; Humans; Intrinsic Factor; Vitamin B 12; Vitamin B 12 Deficiency

Food-cobalamin absorption depends on the initial release of cobalamin from its binders in food. Therefore, the characterization of patients' gastric juices and their behavior in this process was undertaken. Pentagastrin-stimulated gastric juice specimens from three patients with severe food-cobalamin malabsorption, six patients with mild malabsorption, and five patients with normal absorption were tested for pH, pepsin, intrinsic factor content, and an in vitro method that quantitates transfer of cobalamin from egg yolk to gastric R binder. Transfer of cobalamin correlated best with in vivo egg yolk-cobalamin absorption test results in the 14 patients (r = 0.731, P < 0.005). Transfer also correlated inversely with gastric juice pH (r = -0.619, P < 0.02). Basal gastric juice specimens, with their higher pH, from the same subjects failed to promote cobalamin transfer until their pH was lowered to 1.0-1.3. Pepsin levels did not correlate with in vitro transfer or with absorption in vivo; nevertheless, raising the low pepsin concentration of one stimulated gastric juice improved transfer, while inhibiting pepsin activity with pepstatin A inhibited transfer. Mixing experiments with selected stimulated gastric juices demonstrated that poor in vitro transfer, which in a few cases seemed unrelated to pH or pepsin levels, was not due to any inhibitory activity of such gastric juices. These studies confirm that gastric acid and pepsin play a central role in releasing food-bound cobalamin and transferring it to R binder, but suggest that other, still unidentified gastric defects occasionally contribute to impaired transfer; the latter defects are not inhibitory in nature but seem to involve the absence of a permissive activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Gastric Juice; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Intrinsic Factor; Malabsorption Syndromes; Pentagastrin; Pepsin A; Schilling Test; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

To determine whether the increased prevalence of low serum cobalamin concentrations in elderly people represents true deficiency, serum concentrations of cobalamin and folate and of metabolites that are sensitive indicators of cobalamin deficiency were measured in 548 surviving members of the original Framingham Study cohort. Serum cobalamin concentrations < 258 pmol/L were found in 222 subjects (40.5%) compared with 17.9% of younger control subjects (P < 0.001). Serum methylmalonic acid and total homocysteine concentrations were markedly elevated in association with cobalamin values < 258 pmol/L in 11.3% and 5.7%, respectively, of the cohort. Both metabolites were increased in 3.8% of the cohort, associated with significantly lower erythrocyte counts and higher mean cell volumes. Serum metabolites correlated best with serum cobalamin values, even when subnormal determinations were excluded. The prevalence of cobalamin deficiency was > or = 12% in a large sample of free-living elderly Americans. Many elderly people with "normal" serum vitamin concentrations are metabolically deficient in cobalamin or folate.

Topics: Adult; Aged; Aged, 80 and over; Aging; Cohort Studies; Female; Folic Acid Deficiency; Gas Chromatography-Mass Spectrometry; Homocysteine; Humans; Intrinsic Factor; Male; Massachusetts; Methylmalonic Acid; Middle Aged; Prevalence; Radioimmunoassay; Reference Values; Surveys and Questionnaires; Vitamin B 12 Deficiency

As the co-existence of pernicious anaemia (PA) and systemic lupus erythematosus (SLE) has been repeatedly reported, we have investigated the presence of anti-intrinsic factor antibodies (IFAb), the immunological hallmark of PA, in patients diagnosed with SLE. Serum cobalamin levels and IFAb were determined in 30 women diagnosed with SLE as well as in 45 controls. Cobalamin levels were low in 7/30 patients. IFAb were detected in 3/30 sera from patients but in none of the control sera. The presence of IFAb was associated with a low cobalamin concentration, anaemia and macrocytosis in only one patient. There was no evident relationship between the presence of IFAb and serological markers of SLE. We conclude that IFAb may appear in SLE patients, although the cobalamin deficiency described in SLE seems to be due to the presence of IFAb in only a minority of cases.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies; Female; Fluorescent Antibody Technique; Hemoglobins; Humans; Immunodiffusion; Intrinsic Factor; Lupus Erythematosus, Systemic; Middle Aged; Schilling Test; Vitamin B 12; Vitamin B 12 Deficiency

Ten cases of pernicious anaemia seen over a 15-year period (1973-1988) in a Lagos hospital are presented. Their ages ranged from 34 to 67 with a mean of 53.6 years. Females outnumbered males 6 to 4. Complications seen include gastric carcinoma, myelopathy, peripheral neuropathy, skin hyperpigmentation, hair depigmentation and diarrhoea. Reluctance to consider the diagnosis owing to firmly held notions of its rarity and a penchant for empirically treating chronic anaemias with all available haematinics and blood transfusion are probably contributory to its underdiagnosis. The fact that seven of the patients presented were seen in the last three years and three of them in the last one year raises the possibility of an increasing incidence of pernicious anaemia in Africans. The disease may be much less rare in Africans than once believed, and medical education should emphasize its existence and advocate greater care in the management of chronic anaemias.

Topics: Achlorhydria; Adult; Aged; Anemia, Pernicious; Autoantibodies; Autoimmune Diseases; Bone Marrow; Diagnosis, Differential; Fatigue; Female; Humans; Hydroxocobalamin; Incidence; Intrinsic Factor; Male; Middle Aged; Nigeria; Peripheral Nervous System Diseases; Pigmentation Disorders; Psychophysiologic Disorders; Retrospective Studies; Vitamin B 12; Vitamin B 12 Deficiency

Vitamin B-12 deficiency was diagnosed in a 26-year-old man. Examinations performed to determine the etiology of the deficiency showed a vitamin B-12 malabsorption in the Schilling test which was corrected by adding intrinsic factor (IF) as well as normal gastric mucosa and acid secretion, although IF in gastric juice was absent. Family study showed normal serum vitamin B-12 levels in the parents, who are first cousins, and siblings. A gastric examination in the father and the sister showed decreased IF secretion, indicating heterozygosity for the disorder.

Topics: Adult; Anemia, Pernicious; Heterozygote; Humans; Intrinsic Factor; Male; Pedigree; Spain; Vitamin B 12 Deficiency

To assess the prevalence and clinico-biologic characteristics of pernicious anaemia (PA) showing subtle or atypical onset.. One-hundred and twenty-four patients were found to fulfill criteria for PA (serum vitamin B12 deficiency due to absence of intrinsic factor secretion because of severe gastric atrophy). Of them were disclosed those lacking macrocytosis (MCV less than 98 fL), with or without anaemia (Hb less than 120 g/L in women and less than 14 f/L in men), but showing decreased serum B12 rates (less than 150 pmol/L).. Macrocytosis was absent in 15 out of the 124 cases (12.1%); either they had anaemia or not, serum B12 rates were decreased in all cases. Eight patients had concurrent iron deficiency, one had secondary anaemia, two had polycythaemia and four were normal from a haematological standpoint. Serum B12 assays were performed because of neuropsychiatric impairment (2 cases), polycythaemia study (3 cases), or positive anti-parietal cell antibodies found in an immunologic study (4 cases). The remaining patients were studied for chronic atrophy of the gastric mucosa (2 cases), and Plummer-Vinson syndrome, leucopenia and nutritional assessment (1 case of each condition).. Atypical presentation of pernicious anaemia, whose frequency is probably underestimated, was confirmed in our environment. This condition must be suspected and ruled out in patients with characteristics similar to those described above.

Topics: Anemia, Hypochromic; Anemia, Pernicious; Chronic Disease; Diagnosis, Differential; Gastritis, Atrophic; Humans; Intrinsic Factor; Iron Deficiencies; Polycythemia; Prevalence; Retrospective Studies; Vitamin B 12 Deficiency

Inherited selective intestinal malabsorption of cobalamin (Cbl) was observed in a family of giant schnauzer dogs. Family studies and breeding experiments demonstrated simple autosomal recessive inheritance of this disease. Affected puppies exhibited chronic inappetence and failure to thrive beginning between 6 and 12 wk of age. Neutropenia with hypersegmentation, anemia with anisocytosis and poikilocytosis, and megaloblastic changes of the bone marrow were present. Serum Cbl concentrations were low, and methylmalonic aciduria and homocysteinemia were present. Parenteral, but not oral, cyanocobalamin administration rapidly eliminated all signs of Cbl deficiency except for low serum Cbl concentrations. Cbl malabsorption in affected dogs was documented by oral administration of [57Co]cyanocobalamin with or without simultaneous oral administration of intrinsic factor or normal dog gastric juice. Quantitation and function studies of intrinsic factor and transcobalamin-II from affected dogs revealed no abnormality. Other gastrointestinal functions and ileal morphology were normal, indicating a selective defect of Cbl absorption at the level of the ileal enterocyte. Immunoelectron microscopy of ileal biopsies showed that the receptor for intrinsic factor-Cbl complex was absent from the apical brush border microvillus pits of affected dogs. This canine disorder resembles inherited selective intestinal Cbl malabsorption (Imerslund-Gräsbeck syndrome) in humans, and is a spontaneously occurring animal model of early onset Cbl deficiency.

Topics: Animals; Dog Diseases; Dogs; Female; Genes, Recessive; Ileum; Intrinsic Factor; Malabsorption Syndromes; Male; Methylmalonic Acid; Pedigree; Receptors, Cell Surface; Vitamin B 12; Vitamin B 12 Deficiency

It is possible that the commonly measured serum level of vitamin B12 may miss some cases when used to detect vitamin B12 malabsorption and deficiency in older persons. Serum levels of vitamin B12 and intrinsic factor antibody (IFAB) were determined on 250 consecutive patients over the age of 70 admitted to a rehabilitation hospital. Patients with abnormal results on either test were given the standard Schilling test when possible. Eight patients had documented B12 malabsorption. Of these, five had a low serum B12 level alone and one had a low serum B12 level and a positive IFAB level; however, two patients had positive IFAB and normal serum B12 levels. Serum IFAB level may serve as a useful adjunct to serum B12 level in detecting vitamin B12 malabsorption in older patients.

Topics: Aged; Antibodies; Female; Humans; Intrinsic Factor; Male; Prevalence; Prospective Studies; Rehabilitation Centers; Schilling Test; Vitamin B 12; Vitamin B 12 Deficiency

Abnormally low serum cobalamin levels (less than 180 pg/ml) have been observed in 154 of 429 patients (36%) at an average of 22 months (range 3-64 months) after gastric bypass surgery for morbid obesity. Twenty-four patients underwent a Schilling test and retrograde endoscopy of the bypassed gastric segment to determine the presence of intrinsic factor (IF) in gastric aspirates and in mucosal biopsies at 22 +/- 4 months after surgery. Five patients had a normal cobalamin level (405 +/- 44 pg/ml), and gastric juice intrinsic factor was present in three of them (11 +/- 7 ng/ml). Nineteen patients had a low cobalamin level (113 +/- 8 pg/ml), and gastric juice IF was found in only two subjects of this group (10 ng/ml each). Basal gastric juice IF concentration of healthy control subjects was 24 +/- 5 ng/ml. Schilling test results were normal in all five patients of the first group and in only nine patients of the group with cobalamin deficiency after surgery. To assess whether IF was present within the parietal cells of subjects with absent luminal IF, we studied gastric biopsy material of 14 patients using a well-characterized indirect immunoperoxidase method. IF was identified in fundic mucosal biopsy specimens of all 14 patients with absent gastric juice IF. We conclude that cobalamin deficiency occurs in a significant number of patients after gastric bypass and is associated with absence of gastric juice IF. We propose that this abnormality might be caused by inadequate secretion of IF from the bypassed stomach.

Topics: Adult; Female; Gastric Bypass; Gastric Juice; Gastric Mucosa; Humans; Immunoenzyme Techniques; Intrinsic Factor; Male; Obesity, Morbid; Schilling Test; Vitamin B 12 Deficiency

A protein-bound Schilling test incorporating chick serum was used to study 16 elderly vitamin B12-deficient inpatients. Thirteen of these also underwent standard Schilling tests. They were compared with an age-matched control group of non-deficient inpatients. The lower limit of normal for assimilation of protein-bound vitamin B12 was 0.7%. Fourteen out of 16 deficient patients assimilated protein-bound vitamin B12 subnormally. Twelve of these were fully Schilling tested. Five assimilated free B12 normally, and five responded to intrinsic factor. One patient did not respond to intrinsic factor and had jejunal diverticulosis and one could not be categorized. One of two patients with normal assimilation had a borderline vitamin B12 intake. No subjects had neurological sequelae and only three were anaemic. In this population, B12 deficiency is usually asymptomatic but nearly always results from impaired assimilation possibly justifying replacement therapy. Schilling testing only affects treatment if there is other evidence of small-bowel dysfunction.

Topics: Age Factors; Aged; Aged, 80 and over; Carrier Proteins; Female; Ferritins; Folic Acid; Humans; Intrinsic Factor; Male; Middle Aged; Random Allocation; Schilling Test; Vitamin B 12 Deficiency

Three familial cases of congenital intrinsic factor deficiency are reported: the stress is put on the interest of gastric investigations and especially of the quantity of intrinsic factor in the gastric juice when investigating megaloblastic anemia due to vitamin B12 deficiency. The study of the level of intrinsic factor in the gastric juice is proposed as a test for identifying carriers.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Child, Preschool; Female; Gastric Juice; Genetic Carrier Screening; Humans; Infant; Intrinsic Factor; Vitamin B 12 Deficiency

A case of pernicious anemia in a 30 years old men is described. This disease was typical for the hematologic, immunologic and medullary patterns, for his evolution, but the Schilling test, a dual tracer method, did not confirm the diagnosis. The contradictory of this result can be explained wether by the bias of the test itself, or by the intestinal malabsorption due to the vitamin B12 deficiency, or by other factors like bacterial overgrowth state (associated in the pernicious anemia) and a high level of antibodies to intrinsic factor.

Topics: Adult; Anemia, Pernicious; False Negative Reactions; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Schilling Test; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adolescent; Anemia, Macrocytic; Follow-Up Studies; Humans; Intestinal Absorption; Intrinsic Factor; Lymphangiectasis, Intestinal; Malabsorption Syndromes; Male; Protein-Losing Enteropathies; Proteinuria; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adult; Aged; Aged, 80 and over; Anemia, Pernicious; Autoimmune Diseases; Female; Humans; Intrinsic Factor; Male; Middle Aged; Spain; Stomach Diseases; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Humans; Intrinsic Factor; Schilling Test; Vitamin B 12 Deficiency

The ratio of pepsinogen I to pepsinogen II in the circulation decreases progressively with increasing severity of atrophic gastritis of the fundic gland mucosa. Fasting blood was obtained from 359 free-living and institutionalized elderly people (age range, 60 to 99 years). A pepsinogen I/pepsinogen II ratio less than 2.9, indicating atrophic gastritis, was found in 113 (31.5%) subjects. The prevalence of atrophic gastritis increased significantly with advancing age (P less than .05). Within the atrophic gastritis group, 84 had a pepsinogen I level greater than or equal to 20 micrograms/L, indicating mild to moderate atrophic gastritis, and 29 had a pepsinogen I level less than 20 micrograms/L, indicating severe atrophic gastritis or gastric atrophy. A significant increase in the prevalences of elevated serum gastrin levels (P less than .005), low serum vitamin B12 levels (P less than .005), circulating intrinsic factor antibody (P less than .005), and anemia (P less than .025) was observed with stepwise increases in severity of atrophic gastritis. Subjects with atrophic gastritis exhibited a lower mean serum vitamin B12 level (P less than .05) and a higher mean folate level (P less than .05), but no difference was detected in mean hemoglobin levels or serum levels of iron, ferritin, retinol or alpha-tocopherol. It is concluded that serum pepsinogen I and pepsinogen II levels can be used to determine the prevalence and severity of atrophic gastritis, that atrophic gastritis is common in an elderly population, and that atrophic gastritis is associated with vitamin B12 deficiency and anemia. Further, higher folate levels in atrophic gastritis may be related to an accumulation of 5-methyl tetrahydrofolate in serum due to vitamin B12 deficiency and/or greater folate synthesis by the intestinal flora resulting from bacterial overgrowth secondary to hypo- or achlorhydria.

Topics: Aged; Aged, 80 and over; Aging; Boston; Female; Gastrins; Gastritis; Gastritis, Atrophic; Hemoglobins; Humans; Intrinsic Factor; Male; Middle Aged; Nutritional Status; Pepsinogens; Vitamin B 12 Deficiency

A middle-aged woman developed a postgastric bypass megaloblastic anemia which responded to treatment. She eventually had the bypass reversed 6 1/2 yr after it had been performed. Gastric parietal cell function has remained abnormal almost 3 yr after reversal of the bypass, as demonstrated by abnormal Schilling tests and high serum gastrin levels. Parietal cell antibodies in high titer, but no intrinsic factor antibodies, were demonstrated in her blood. These observations are interpreted as indicating the development of irreversible chronic atrophic gastritis probably related to reflux of bile into the bypassed stomach.

Topics: Adult; Anemia, Megaloblastic; Female; Gastric Acid; Gastrins; Humans; Intrinsic Factor; Parietal Cells, Gastric; Postoperative Complications; Stomach; Vitamin B 12 Deficiency

One of the diverse group of disorders that cause pernicious anemia in childhood, juvenile pernicious anemia, has been characterized by normal acid secretion, normal gastric mucosal histology, adequate intestinal absorption of cobalamin in the presence of exogenous gastric intrinsic factor (IF), but the inadequate "production" of IF from birth. Inadequate production has been inferred from the absence of measured IF in stimulated gastric secretions. To assess whether immunogenic IF was commonly present within the parietal cells of subjects with juvenile pernicious anemia, we studied paraffin-embedded biopsy material from the largest reported series of childhood pernicious anemia, using a well-characterized indirect immunoperoxidase method. Preliminary studies were able to identify IF in fundic mucosal biopsy specimens that had been stored for as long as 27 yr. In a blinded evaluation, six of the nine fundic biopsy specimens from children with juvenile pernicious anemia demonstrated immunogenic IF. Two sets of siblings were concordant for the presence or absence of intracellular IF, and six gastric biopsy specimens from patients with Imerslund's syndrome were all positive for IF. These findings indicate that juvenile pernicious anemia is a heterogeneous group of disorders whose similar clinical expression might be caused by (a) inadequate synthesis of IF, (b) a block in IF secretion, (c) the secretion of an abnormal IF that does not bind to cobalamin, or (d) the secretion of other abnormal IFs that could contain a number of other functional defects.

Topics: Anemia, Pernicious; Child, Preschool; Gastric Fundus; Histocytochemistry; Humans; Immunoenzyme Techniques; Intrinsic Factor; Malabsorption Syndromes; Parietal Cells, Gastric; Retrospective Studies; Vitamin B 12 Deficiency

Topics: Child, Preschool; Diagnosis, Differential; Female; Humans; Infant; Intrinsic Factor; Malabsorption Syndromes; Male; Schilling Test; Vitamin B 12 Deficiency

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: Adolescent; Anemia, Megaloblastic; Child; Child, Preschool; Female; Folic Acid Deficiency; Humans; Infant; Intestinal Absorption; Intrinsic Factor; Male; Transcobalamins; Vitamin B 12 Deficiency

Topics: Anti-Ulcer Agents; Bismuth; Cimetidine; Guanidines; Humans; Intestinal Absorption; Intrinsic Factor; Male; Organometallic Compounds; Peptic Ulcer; Vitamin B 12; Vitamin B 12 Deficiency

A competitive protein binding radioassay kit for serum vitamin B(12) has been assessed. Precision, linearity, sensitivity, and specificity have been found to be satisfactory. Falsely-normal assay results in patients with vitamin B(12) deficiency have not been observed.

Topics: Adolescent; Biological Assay; Female; Humans; Intrinsic Factor; Male; Middle Aged; Radioligand Assay; Reagent Kits, Diagnostic; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Serum vitamin B12 (B12) levels of 53 patients (15 with pernicious anemia) and 42 healthy volunteers were determined using crude intrinsic factor (IF), pure IF, and a mixture of crude IF + R-protein blocking agent (block IF). The radioassay using pure IF showed less sample-to-sample variation in nonspecific binding than the radioassay using block IF. The mean B12 levels in 42 healthy subjects were significantly higher with crude IF (499 +/- 23 pg/ml, 1 s.e.m.) than with pure IF (408 +/- 29 pg/ml) or with block IF (407 +/- 22 pg/ml). B12 levels were abnormally low in all 15 patients with pernicious anemia by pure IF (less than 100 pg/ml), in 14 patients by block IF (less than 150 pg/ml), and in only seven patients by crude IF (less than 200 pg/ml). Our data confirm previous reports that B12 deficiency can be diagnosed more reliably by measuring serum B12 levels with etiher pure IF or block IF.

Topics: Anemia, Pernicious; Humans; In Vitro Techniques; Intrinsic Factor; Protein Binding; Radioimmunoassay; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Humans; Intrinsic Factor; Radioimmunoassay; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Humans; Intestine, Small; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Vitamin B 12; Vitamin B 12 Deficiency

The megaloblastic anaemia observed in patients with chronic atrophic gastritis is usually due to malabsorption of vitamin B12. In some cases, the absence of intrinsic factor supports the diagnosis of pernicious anaemia but other factors, the importance of which varies from case to case, are also involved. They include proliferation of bacteria in the lumen of the gut, intestinal cell abnormalities resulting from lack of vitamin B12 and low hydrochloric acid output with subsequent reduction in the release of vitamin B12 from foodstuffs. With regard to treatment, it would seem justified to combine oral broad-spectrum antibiotics with parenteral administration of vitamin B12.

Topics: Achlorhydria; Aged; Anemia, Megaloblastic; Female; Gastritis; Gastritis, Atrophic; Humans; Intestine, Small; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Gastrointestinal Diseases; Humans; Ileum; Injections; Intrinsic Factor; Male; Middle Aged; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Bone Marrow Cells; DNA; Ferritins; Folic Acid Deficiency; Intestinal Mucosa; Intrinsic Factor; Iron; Myelin Sheath; Schilling Test; Vitamin B 12 Deficiency

Topics: Alcoholism; Celiac Disease; Exocrine Pancreatic Insufficiency; Folic Acid; Folic Acid Deficiency; Gastric Mucosa; Glutamates; Humans; Ileum; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Protein Binding; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Protein- (chicken serum) bound [57Co]cyanocobalamin absorption was evaluated in five hypochlorhydric patients who had developed B12 deficiency despite having normal absorption of unbound crystalline vitamin B12. All five patients had decreased urinary excretion of protein-bound B12 (0.06--0.34%) as compared to twelve normal controls (0.61--5.6%), P less than .001. Improvement in protein-bound B12 absorption in four of the five patients occurred with the exogenous administration of hydrochloric acid, pepsin, gastric intrinsic factor, or a combination thereof. Vitamin B12 deficiency developing in the setting of hypochlorhydria may result from deficiency of acid-peptic digestion of B12 bound to protein and/or a relative deficiency of intrinsic factor. This digestive defect is not detected with tests which measure the absorption of unbound crystalline B12 but is detected by a simple test which employs B12 bound to chicken serum as the form of protein-bound B12.

Topics: Aged; Female; Gastrectomy; Humans; Hydrochloric Acid; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Pepsin A; Protein Binding; Vitamin B 12; Vitamin B 12 Deficiency

Human bile incubated with vitamin B12 bound to intrinsic factor in human gastric juice will effectively dissociate this complex, and the vitamin will transfer to non-intrinsic factor unsaturated binding protein(s) contained in bile. Preincubation of the bile with pancreatic enzymes, particularly trypsin, and pepsin, decreases this effect of bile on the intrinsic factor--vitamin B12 complex by digesting the unsaturated binder(s) in the bile. These studies help explain why there is malabsorption of tracer amounts of vitamin B12 in some patients with pancreatic insufficiency, and why this abnormality is correctable by the administration of pancreatic extract.

Topics: Bile; Humans; Intrinsic Factor; Malabsorption Syndromes; Pancreatic Diseases; Pepsin A; Trypsin; Vitamin B 12; Vitamin B 12 Deficiency

Myasthenia gravis (MG) is an autoimmune disease often associated with other autoimmune disorders. A case history of MG with a coexisting atypical megaloblastic anaemia with vitamin B12 deficiency and anti Intrinsic Factor (IF) antibodies, led to a study of humoral and cellular immunity to IF in 81 MG patients. Within this series, 3 other patients had a disturbed humoral and cellular immunity to IF. These 3 patients presented no other features of pernicious anaemia. The possible origins and significance of the anti IF antibodies in MG patients are discussed.

Topics: Adolescent; Adult; Aged; Anemia, Macrocytic; Anemia, Megaloblastic; Antibodies; Antibody Formation; Child; Female; Humans; Immunity, Cellular; Immunologic Techniques; Intrinsic Factor; Male; Middle Aged; Myasthenia Gravis; Vitamin B 12 Deficiency

Colchicine can induce the malabsorption of vitamin B12 and other nutrients. Previous investigations have suggested but not proved that this malabsorption was due to a lesion in the ileal mucosa. Employing the receptor assay of M. Katz and B. A. Cooper (J Clin Invest 54:733-739, 1974), the authors have observed a dose-related, reversible reduction in the quantity of intrinsic factor-vitamin B12 (IF-B12) receptor (from 5.78 ng to 1.3 ng of B12 binding) in the intestinal mucosa of guinea pigs fed 0.05-0.25 mg/100 g colchicine/day for 3 days. Malabsorption of vitamin B12 was also demonstrated in vivo in similarly treated animals. Increasing intestinal motility with cascara sagrada had no effect on the IF-B12 receptor. The quantity of IF-B12 receptor and the amount of vitamin B12 absorbed increased markedly to greater than normal levels during recovery from a 3-day course of colchicine. The total number of intestinal cells decreased after colchicine administration and increased during recovery; however, the fluctuations observed were not sufficient to explain the changes in the quantity of receptor. Histologic examination of the ileal mucosa showed a decrease in the population of villus cells after colchicine. The correlation between the changes in receptor quantity and in vivo B12-absorption prove that the IF-B12 receptor is a critical limiting factor in B12 absorption.

Topics: Animals; Colchicine; Depression, Chemical; DNA; Dose-Response Relationship, Drug; Female; Guinea Pigs; Intestinal Absorption; Intestinal Mucosa; Intestine, Small; Intrinsic Factor; Receptors, Drug; Vitamin B 12; Vitamin B 12 Deficiency

Since R protein binds cobalamin (vitamin B12) and cobalamin analogues, whereas intrinsic factor is highly specific for true cobalamin, we compared the serum cobalamin values obtained with these proteins in radioisotope dilution assays. With R protein, eight of 21 patients with cobalamin deficiency had serum cobalamin levels (mean, 204, range, 85 to 355 pg per milliliter) that overlapped with values for 74 normal subjects (mean, 576, range, 220 to 1230). With intrinsic factor, no patient values (mean, 36, range, less than 10 to 78 pg per milliliter) overlapped with the normal values (mean, 322, range, 130 to 785). Paper chromatography showed that these differences were due to the presence of cobalamin analogues. R protein constituted 51 to 85 per cent of the cobalamin-binding protein in 10 commercial serum cobalamin assay kits, which were said to contain "intrinsic factor". Human plasma contains cobalamin analogues that can mask cobalamin deficiency with current radioisotope dilution assays.

Topics: Adult; Chromatography, Paper; Cobalt Radioisotopes; Diagnostic Errors; Female; Humans; Intrinsic Factor; Male; Middle Aged; Protein Binding; Radioisotope Dilution Technique; Reagent Kits, Diagnostic; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

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

Topics: Biological Availability; Child; Child, Preschool; Cobalt Radioisotopes; Cystic Fibrosis; Dietary Proteins; Food; Humans; Intestinal Absorption; Intrinsic Factor; Iron; Iron Radioisotopes; Liver; Meat; Pancreatin; Protein Binding; Radioisotopes; Selenium; Selenomethionine; Vitamin B 12; Vitamin B 12 Deficiency; Whole-Body Counting

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 otherwise typical addisonian pernicious anaemia and serum anti-intrinsic-factor antibody failed to respond to oral intrinsic factor on repeated testing during three years of therapy with parenteral vitamin B 12. There was no evidence of generalised malaborption. To test the hypothesis that binding of intrinsic factor to gut secretory antibody was responsible, an "augmented" Schilling test was devised using eight times the usual dose of intrinsic factor. This increased dose of intrinsic factor resulted in normal absorption of the test dose of vitamin B 12 confirming the diagnosis. It is suggested that the augmented Schilling test may be useful in the diagnosis of the occasional patient with features of pernicious anaemia who fails to respond to conventional doses of intrinsic factor in the Schilling test.

Topics: Administration, Oral; Adult; Anemia, Pernicious; Autoantibodies; Binding Sites, Antibody; Diagnosis, Differential; Female; Humans; Intrinsic Factor; Malabsorption Syndromes; Schilling Test; Vitamin B 12 Deficiency

Addisonian pernicious anemia (PA) usually develops after age 50. These PA patients are immunocompetent and usually manifest gastric autoimmunity. The prevalence of PA is increased about 10-fold with multiple myeloma and 250-fold in adults with primary immunoglobulin deficiency. Atrophic gastritis develops at an unusually early age with primary immunoglobulin deficiency but not with myeloma. Family history with myeloma is often relevant to PA. Atrophic gastritis develops in both syndromes without gastrict autoantibody production.

Topics: Aging; Anemia, Pernicious; Antibodies; Binding, Competitive; Child, Preschool; Fluorescent Antibody Technique; Gastric Juice; Gastric Mucosa; Gastritis; Hemagglutination Tests; Humans; Hypersensitivity, Delayed; Immunodiffusion; Immunoglobulins; Infant; Intestinal Secretions; Intrinsic Factor; Multiple Myeloma; Radioimmunoassay; Thyroid Gland; 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: Adult; Female; Gastric Acidity Determination; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Multiple Sclerosis; Schilling Test; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Animals; Biological Assay; Blood Proteins; Chickens; Cobalt Radioisotopes; Euglena gracilis; Female; Folic Acid Deficiency; Humans; Intrinsic Factor; Lactobacillus; Leukemia, Myeloid; Polycythemia Vera; Postgastrectomy Syndromes; Pregnancy; Protein Binding; Radioisotope Dilution Technique; Umbilical Cord; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Blood Specimen Collection; Cobalt Radioisotopes; Diagnostic Errors; Evaluation Studies as Topic; Granulocytes; Humans; Intrinsic Factor; Schilling Test; Vitamin B 12; Vitamin B 12 Deficiency; Whole-Body Counting

Topics: Afferent Loop Syndrome; Anemia, Macrocytic; Diarrhea; Dumping Syndrome; Folic Acid Deficiency; Gastrectomy; Gastric Juice; Gastrins; Humans; Intestinal Absorption; Intrinsic Factor; Mucus; Osteoporosis; Postgastrectomy Syndromes; Stomach Neoplasms; Vitamin B 12 Deficiency; Vomiting

Topics: Anemia, Pernicious; Humans; Intrinsic Factor; Schilling Test; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Administration, Oral; Adult; Anemia, Macrocytic; Anemia, Megaloblastic; Female; Humans; Intrinsic Factor; Peutz-Jeghers Syndrome; Tetracycline; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Humans; Intrinsic Factor; Leiomyoma; Male; Middle Aged; Muscle, Smooth; Remission, Spontaneous; Schilling Test; Stomach Neoplasms; Vitamin B 12; Vitamin B 12 Deficiency; Vitiligo

Topics: Adolescent; Adult; Agammaglobulinemia; Anemia, Macrocytic; Anemia, Megaloblastic; Antibody Formation; Chronic Disease; Female; Gastric Juice; Humans; Immunoglobulin A; Immunoglobulin G; Immunologic Deficiency Syndromes; Intrinsic Factor; Malabsorption Syndromes; Male; Proteinuria; Syndrome; Vitamin B 12 Deficiency

Topics: Adolescent; Anemia, Macrocytic; Anemia, Pernicious; Chronic Disease; Consanguinity; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Recurrence; Vitamin B 12 Deficiency

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, Pernicious; Female; Folic Acid Deficiency; Humans; Intrinsic Factor; Male; Middle Aged; Schilling Test; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Biopsy; Body Weight; Dumping Syndrome; Duodenal Ulcer; Dyspepsia; Female; Follow-Up Studies; Gastrectomy; Gastric Mucosa; Hemoglobins; Humans; Intestinal Absorption; Intrinsic Factor; Iron; Male; Postgastrectomy Syndromes; Schilling Test; Stomach Ulcer; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Administration, Oral; Anemia, Pernicious; Delayed-Action Preparations; Erythrocytes; Hemoglobins; Humans; Hydroxocobalamin; Injections, Intramuscular; Injections, Intravenous; Intrinsic Factor; Postgastrectomy Syndromes; Schilling Test; Time Factors; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Antibodies; Bacteriological Techniques; Bile Acids and Salts; Cells, Cultured; Follow-Up Studies; Humans; Hydrochloric Acid; Ileum; Intestinal Absorption; Intestine, Small; Intrinsic Factor; Jejunum; Obesity; Schilling Test; Tetracycline; Time Factors; Vitamin B 12; Vitamin B 12 Deficiency

Two siblings with megaloblastic anemia responsive to parenteral vitamin B(12) were studied to elucidate the cause of the B(12) deficiency. Gastric juice from both contained acid and functional intrinsic factor. Serum contained transcobalamin II and lacked antibodies to intrinsic factor. Schilling tests showed vitamin B(12) malabsorption uncorrected by hog intrinsic factor or pancreatic extract. Other parameters of small intestinal function were normal. Proteinuria was initially present in both but cleared in one following treatment with B(12). These patients with "familial selective vitamin B(12) malabsorption" are the first reported from Canada. Only 37 cases have been reported in the world literature to date.

Topics: Anemia, Macrocytic; Child; Child, Preschool; Cobalt Radioisotopes; Female; Follow-Up Studies; Gastric Juice; Humans; Intestinal Absorption; Intrinsic Factor; Male; Schilling Test; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adolescent; Adult; Aged; Alcoholism; Anemia, Pernicious; Diagnostic Errors; Female; Folic Acid; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Retrospective Studies; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adolescent; Adult; Agglutination; Anemia, Pernicious; Animals; Antibodies; Antibodies, Antinuclear; Child; Cobalt Radioisotopes; Female; Fluorescent Antibody Technique; Gastric Mucosa; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Schilling Test; Swine; Thyroid Gland; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Cell Nucleus; Child; Female; Humans; Intrinsic Factor; Pigmentation Disorders; Skin; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Animals; Fasting; Gastrectomy; Gastric Acidity Determination; Gastric Juice; Gastrointestinal Hormones; Injections, Intraperitoneal; Intrinsic Factor; Male; Parabiosis; Rats; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Female; Fetus; Glycoproteins; Humans; Ileum; Intrinsic Factor; Malabsorption Syndromes; Pregnancy; Protein Binding; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia; Binding, Competitive; Blood Proteins; Cellulose; Cobalt Radioisotopes; Dextrans; Evaluation Studies as Topic; Humans; Intrinsic Factor; Isotope Labeling; Methods; Protein Binding; Radiochemistry; Regression Analysis; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia; Anemia, Hypochromic; Anemia, Pernicious; Anemia, Sideroblastic; Blind Loop Syndrome; Crohn Disease; Diverticulitis; Folic Acid Deficiency; Gastritis; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Gastrointestinal Neoplasms; Humans; Intrinsic Factor; Malabsorption Syndromes; Vitamin B 12 Deficiency; Whipple Disease

Topics: Anemia, Pernicious; Antibody Specificity; Autoantibodies; Blood Transfusion; Chromium Isotopes; Erythrocyte Aging; Hemolysis; Humans; Intrinsic Factor; Splenomegaly; Time Factors; Vitamin B 12 Deficiency

Topics: Adult; Anemia, Pernicious; Diet; Female; Humans; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Male; Nutritional Physiological Phenomena; Nutritional Requirements; Pregnancy; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adolescent; Anemia, Macrocytic; Humans; Immunologic Deficiency Syndromes; Intrinsic Factor; Malabsorption Syndromes; Male; Proteinuria; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Animals; Bacteria; Blind Loop Syndrome; Cobalt Isotopes; Culture Media; Gastric Juice; Intestinal Absorption; Intrinsic Factor; Jejunum; Malabsorption Syndromes; Male; Methods; Neomycin; Rats; Tetracycline; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Aminosalicylic Acids; Cobalt Isotopes; Humans; Hydrogen-Ion Concentration; Ileum; Intestinal Absorption; Intrinsic Factor; Schilling Test; Telemetry; Tuberculosis, Pulmonary; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adult; Age Factors; Aged; Alcohol Drinking; Duodenal Ulcer; Erythrocytes; Follow-Up Studies; Gastrectomy; Gastric Juice; Humans; Intrinsic Factor; Leiomyoma; Methods; Middle Aged; Pepsin A; Postoperative Complications; Schilling Test; Stomach Neoplasms; Stomach Ulcer; Time Factors; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Chemical Phenomena; Chemistry; Coenzymes; Humans; Ileum; Intestinal Absorption; Intrinsic Factor; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Achlorhydria; Adult; Aged; Anemia, Pernicious; Female; Humans; Intrinsic Factor; Male; Middle Aged; Smoking; Stomach Neoplasms; Vitamin B 12 Deficiency

Topics: Adolescent; Adult; Aged; Cobalt Isotopes; Euglena; Humans; Intrinsic Factor; Methods; Middle Aged; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adolescent; Anemia, Macrocytic; Anemia, Pernicious; Diet; Female; Folic Acid Deficiency; Humans; Intrinsic Factor; Male; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Anemia, Pernicious; Anticonvulsants; Ascorbic Acid Deficiency; Contraceptives, Oral; Diagnosis, Differential; Folic Acid; Folic Acid Deficiency; Gastric Juice; Humans; Intrinsic Factor; Nutritional Requirements; Schilling Test; Vitamin B 12; Vitamin B 12 Deficiency

A procedure is described for the determination of the separate amounts of two gamma-emitting radioisotopes present simultaneously in large liquid volumes using an annular cell placed over a standard well-type crystal of sodium iodide and a reference source of (137)Cs. This sensitive technique is illustrated with particular reference to the double radioisotope urinary excretion test, using orally administered (57)CoB(12) bound to human gastric juice and (58)CoB(12) simultaneously, for the differentiation between patients with intrinsic factor deficiency and other causes of vitamin B(12) malabsorption.

Topics: Cesium Isotopes; Cobalt Isotopes; Humans; Intestinal Absorption; Intrinsic Factor; Iodides; Mathematics; Methods; Radiometry; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adult; Aged; Anemia, Macrocytic; Anemia, Pernicious; Child, Preschool; Diagnosis, Differential; Female; Gastric Juice; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Schilling Test; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Anemia, Pernicious; Antibody Formation; Autoantibodies; Autoimmune Diseases; Cell Migration Inhibition; Gastric Juice; Humans; Intestinal Absorption; Intrinsic Factor; Nutritional Requirements; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Folic Acid Deficiency; Humans; Intellectual Disability; Intestinal Absorption; Intrinsic Factor; Metabolism, Inborn Errors; Orotic Acid; Transferases; Vitamin B 12 Deficiency

Topics: Gastric Juice; Humans; Intrinsic Factor; Malabsorption Syndromes; Vitamin B 12 Deficiency

Topics: Adolescent; Adult; Aged; Biological Assay; Cobalt Isotopes; Female; Humans; Intrinsic Factor; Lactobacillus; Male; Methods; Middle Aged; Protein Binding; Radioisotope Dilution Technique; Vitamin B 12; Vitamin B 12 Deficiency

Three patients are described, and they provide further evidence that deficiency of folic acid and vitamin B(12) may sometimes affect small intestinal function. Malabsorption of both xylose and vitamin B(12) returned to normal in one patient after treatment of a megaloblastic anaemia due to dietary deficiency of folic acid. Impaired absorption of vitamin B(12) was corrected by vitamin B(12) therapy in the other two patients. The initial cause of the vitamin B(12) deficiency in one patient was not apparent, but she was taking Gynovlar 21, which may have been an aetiological factor. In the third patient the small intestinal defect was secondary to pernicious anaemia, and in a group of 98 other patients with pernicious anaemia intrinsic factor did not improve vitamin B(12) absorption in six, and only partially corrected absorption in 30. The significance of these observations is discussed.

Topics: Adult; Anemia, Macrocytic; Anemia, Pernicious; Contraceptives, Oral; Female; Folic Acid; Folic Acid Deficiency; Humans; Intestinal Absorption; Intestine, Small; Intrinsic Factor; Malabsorption Syndromes; Vitamin B 12; Vitamin B 12 Deficiency; Xylose

Topics: Anemia, Pernicious; Cobalt Isotopes; Diagnosis, Differential; Humans; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Radionuclide Imaging; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Affective Symptoms; Aged; Anemia, Pernicious; Antibodies; Cognition Disorders; Dementia; Female; Folic Acid Deficiency; Gastric Mucosa; Humans; Intracranial Arteriosclerosis; Intrinsic Factor; Male; Mental Disorders; Schilling Test; Vitamin B 12 Deficiency

Topics: Adult; Anemia, Macrocytic; Anemia, Pernicious; Autoantibodies; Blood Cell Count; Diagnosis, Differential; Diphyllobothriasis; Female; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Schilling Test; Time Factors; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Humans; Intrinsic Factor; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adult; Aged; Anemia, Pernicious; Cobalt Isotopes; Humans; Intrinsic Factor; Middle Aged; Schilling Test; Vitamin B 12 Deficiency; Vitiligo

Topics: Adult; Aged; Aged, 80 and over; Anemia, Megaloblastic; Anemia, Pernicious; Antibodies; Arthritis, Rheumatoid; Female; Folic Acid Deficiency; Humans; Intrinsic Factor; Male; Middle Aged; Vitamin B 12 Deficiency

Topics: Achlorhydria; Adult; Aged; Anemia, Macrocytic; Anemia, Pernicious; Black People; Cobalt Isotopes; Female; Folic Acid Deficiency; Humans; Intrinsic Factor; Male; Middle Aged; Radiometry; Vitamin B 12; Vitamin B 12 Deficiency; White People

Topics: Binding Sites; Biological Transport; Intrinsic Factor; Protein Binding; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Anemia, Pernicious; Body Height; Body Weight; Chromosome Aberrations; Chromosome Disorders; Diet Therapy; Female; Genes, Recessive; Growth; Humans; Infant; Infant, Newborn; Intellectual Disability; Intelligence Tests; Intrinsic Factor; Male; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Animals; Autoantibodies; Humans; In Vitro Techniques; Intrinsic Factor; Vitamin B 12; Vitamin B 12 Deficiency

The case histories are given of two patients, aged 38 and 35 years, who conceived while suffering from Addisonian pernicious anaemia. The relationship of these findings to the routine use of folic acid during pregnancy is discussed.

Topics: Adult; Age Factors; Anemia, Pernicious; Female; Fertility; Folic Acid; Humans; Intrinsic Factor; Pregnancy; Pregnancy Complications, Hematologic; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Erythrocyte Count; Humans; Hydroxocobalamin; Intrinsic Factor; Liver Extracts; Reticulocytes; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adult; Bicarbonates; Binding Sites; Celiac Disease; Humans; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Male; Pancreas; Pancreatic Diseases; Pancreatic Extracts; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Animals; Cobalt Isotopes; Humans; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Swine; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Humans; Intrinsic Factor; Schilling Test; Thyroid Diseases; Vitamin B 12; Vitamin B 12 Deficiency; Vitiligo

Topics: Aged; Anemia, Macrocytic; Anemia, Pernicious; Cobalt Isotopes; Female; Gastrectomy; Histamine; Humans; Intestinal Absorption; Intrinsic Factor; Male; Middle Aged; Radiometry; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adult; Aged; Anemia, Pernicious; Female; Gastric Juice; Humans; Injections, Intramuscular; Intestinal Absorption; Intrinsic Factor; Iron; Male; Middle Aged; Schilling Test; Sulfates; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Animals; Child, Preschool; Feces; Female; Humans; Intrinsic Factor; Kidney; Lipids; Malabsorption Syndromes; Schilling Test; Swine; Vitamin B 12 Deficiency; Xylose

Topics: Adult; Anemia, Pernicious; Antibodies; Female; Folic Acid; Gastric Juice; Gastric Mucosa; Humans; Hydrogen-Ion Concentration; Immunoglobulin G; Infant; Infant, Newborn; Infant, Newborn, Diseases; Intrinsic Factor; Male; Maternal-Fetal Exchange; Neutrophils; Pregnancy; Pregnancy Complications, Hematologic; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Cobalt Isotopes; Humans; Intrinsic Factor; Radiometry; Saliva; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Aged; Antibodies; Atrophy; Biopsy; Fluorescent Antibody Technique; Gastric Juice; Gastric Mucosa; Gastritis; Histamine; Humans; Intrinsic Factor; Iron; Male; Middle Aged; Schilling Test; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Anti-Bacterial Agents; Colistin; Erythrocyte Count; Escherichia coli; Female; Gastric Juice; Humans; Intrinsic Factor; Middle Aged; Multiple Sclerosis; Spinal Cord Diseases; Stomach Neoplasms; Vitamin B 12 Deficiency

Topics: Adult; Anemia, Pernicious; Child; Child, Preschool; Chromosome Aberrations; Chromosome Disorders; Diagnosis, Differential; Female; Humans; Ileum; Intestinal Absorption; Intrinsic Factor; Jejunum; Kidney; Male; Proteinuria; Urogenital Abnormalities; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adolescent; Anemia, Macrocytic; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Vitamin B 12 Deficiency

Topics: Achlorhydria; Anemia, Pernicious; Antibodies; Blood; Carotenoids; Humans; In Vitro Techniques; Intrinsic Factor; Malabsorption Syndromes; Schilling Test; Vitamin A; Vitamin B 12; Vitamin B 12 Deficiency; Xylose

Topics: Anemia; Anemia, Pernicious; Diagnosis, Differential; Humans; Intestinal Absorption; Intrinsic Factor; Metabolism; Proteinuria; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Aged; Anemia, Hypochromic; Anemia, Macrocytic; Gastrectomy; Humans; Intrinsic Factor; Iron; Male; 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; Biotin; Humans; Intestines; Intrinsic Factor; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Guinea Pigs; Intestinal Mucosa; Intestine, Small; Intrinsic Factor; Vitamin B 12 Deficiency

Topics: Anemia; Anemia, Pernicious; Diagnosis, Differential; Erythropoiesis; Humans; Intrinsic Factor; Multiple Sclerosis; Paraparesis, Spastic; Vitamin B 12; Vitamin B 12 Deficiency

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, Pernicious; Animals; Animals, Domestic; Corrinoids; Gastric Juice; Intrinsic Factor; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins