hydroxocobalamin and Anemia--Megaloblastic

We describe 2 children with cobalamin G disease, a disorder of vitamin B

Topics: Anemia, Megaloblastic; Blood Chemical Analysis; Blood Transfusion; Child, Preschool; Disease Progression; Early Diagnosis; Failure to Thrive; Hematologic Tests; Humans; Hydroxocobalamin; Infant; Injections, Intramuscular; Male; Prognosis; Risk Assessment; Severity of Illness Index; Thrombotic Microangiopathies; Treatment Outcome; Vitamin B 12 Deficiency

Topics: Anemia, Megaloblastic; Anemia, Pernicious; Erythrocyte Indices; Erythrocytes; Hematinics; Humans; Hydroxocobalamin; Male; Middle Aged

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

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

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

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

Topics: Adult; Anemia, Megaloblastic; Hematinics; Humans; Hydroxocobalamin; Hyperpigmentation; Male; Skin

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

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

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

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

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

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

Topics: Anemia, Megaloblastic; Atrophy; Brain; Consanguinity; Electroencephalography; Female; Humans; Hydroxocobalamin; Infant; Injections, Intramuscular; Magnetic Resonance Imaging; Myoclonus; Neuroprotective Agents; Pancytopenia; Piracetam; Tremor; Vitamin B 12 Deficiency; Vitamin B Complex

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

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

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

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

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

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

We report here a case of megaloblastic anaemia in late pregnancy, which leads us to question whether folate supplements should be recommended in the UK routinely throughout pregnancy and not just in the preconception period and first trimester.

Topics: Adult; Anemia, Megaloblastic; Female; Folic Acid; Folic Acid Deficiency; Humans; Hydroxocobalamin; Pregnancy; Pregnancy Complications, Hematologic; Vitamin B Complex

Topics: Anemia, Megaloblastic; Evoked Potentials, Visual; Humans; Hydroxocobalamin; Magnetic Resonance Imaging; Male; Middle Aged; Paresthesia; Remission Induction; Spinal Cord Diseases; Vitamin B 12 Deficiency

Transcobalamin II is a serum transport protein for vitamin B12. Small variations in TC-II affinity were recently linked to a high homocysteine level and increased frequency of neural tube defects. Complete absence of TC-II or total functional abnormality causes tissue vitamin B12 deficiency resulting in a severe disease with megaloblastic anemia and immunologic and intestinal abnormalities in the first months of life. This condition was described in hereditary autosomal-recessive form. Low serum TC-II without any symptoms or clinical significance was noted in relatives of affected homozygotes.. To study 23 members of a four-generation family with hereditary vitamin B12 deficiency and neurologic disorders.. Thorough neurologic, hematologic and family studies were supplemented by transcobalamin studies in 20 family members.. Partial TC-II deficiency was found in 19 subjects. Apo TC-II (free TC-II unbound to vitamin B12) and total unsaturated B12 binding capacity were low in all tested individuals but one, and holo TC-II (TC-II bound by vitamin B12) was low in all family members. The presentation of the disease was chronic rather than acute. Early signs in children and young adults were dyslexia, decreased IQ, vertigo, plantar clonus and personality disorders. Interestingly, affected children and young adults had normal or slightly decreased serum vitamin B12 levels but were not anemic. Low serum B12 levels were measured in early adulthood. In mid-late adulthood megaloblastic anemia and subacute combined degeneration of the spinal cord were diagnosed. Treatment with B12 injections resulted in a significant improvement. The pedigree is compatible with an autosomal-dominant transmission. This family study suggests a genetic heterogeneity of TC-II deficiency.. We report the first family with a hereditary transmitted condition of low serum TC-II (partial TC-II deficiency) associated with neurologic and mental manifestations in childhood. Partial TC-II deficiency may decrease the amount of stored cobalamin, resulting in increased susceptibility to impaired intestinal delivery of cobalamin and predisposing to clinically expressed megaloblastic anemia at a later age. Partial TC-II deficiency should be suspected in families with megaloblastic anemia and in individuals with neurologic and mental disturbances--despite normal serum vitamin B12 levels. Low serum UBBC and apo TC-II should confirm the diagnosis. Early vitamin B12 therapy may prevent irreversible neurologic damage.

Topics: Adolescent; Adult; Aged; Anemia, Megaloblastic; Child; Female; Hematinics; Humans; Hydroxocobalamin; Infant; Male; Mental Disorders; Middle Aged; Transcobalamins; Vitamin B 12 Deficiency

Topics: Age of Onset; Anemia, Hemolytic; Anemia, Megaloblastic; Blood Transfusion; Child; Child, Preschool; Dementia; Demyelinating Diseases; Diagnostic Errors; Family Health; Female; Gas Chromatography-Mass Spectrometry; Humans; Hydroxocobalamin; Metabolism, Inborn Errors; Methylation; Nuclear Family; Paralysis; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Humans; Hydroxocobalamin; Infant, Newborn; Male; Transcobalamins

Lymphocyte subpopulations and intrinsic factor and gastric parietal cell antibodies have been measured in 23 patients with megaloblastic anaemia who responded to treatment with hydroxocobalamin. The ratio of helper (OKT4) to suppressor (OKT8) lymphocytes was significantly increased in patients with intrinsic factor antibody compared with those who lacked the antibody. No such correlation was found for gastric parietal cell antibody. Alterations in the lymphocyte helper to suppressor (OKT4:OKT8) ratio may be associated with pernicious anaemia.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Antibodies, Monoclonal; Autoantibodies; Humans; Hydroxocobalamin; Intrinsic Factor; Leukocyte Count; Lymphocytes; Parietal Cells, Gastric; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

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

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

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

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

A case of hereditary transcobalamin II deficiency with neurological involvement is described. The patient presented in early infancy with megaloblastic anaemia and was treated with folinic acid from 6 weeks of age. The diagnosis of transcobalamin II deficiency was not made until he was 2 years old when he showed severely retarded intellectual development, ataxia and pyramidal deficit in the limbs. Following treatment with hydroxocobalamin, his condition has slowly improved but he has remained with a severe neurological deficit. The consequences of vitamin B12 deficiency on neurological development in infancy are discussed.

Topics: Age Factors; Anemia, Macrocytic; Anemia, Megaloblastic; Blood Proteins; Child; Genes, Recessive; Humans; Hydroxocobalamin; Intellectual Disability; Male; Nervous System Diseases; Transcobalamins; Vitamin B 12 Deficiency

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

Topics: Anemia, Megaloblastic; Deoxyuridine; DNA; Female; Homocysteine; Homocystinuria; Humans; Hydroxocobalamin; Infant; Infant, Newborn; Malonates; Methionine; Methylmalonic Acid; Myoclonus; Thymidine

Folate analogues were added to human bone marrow cells to determine their effect on deoxyuridine utilization in the deoxyuridine suppression test. Formyltetrahydrofolates fully corrected the impairment of dU utilization in pernicious anaemia marrows but tetrahydrofolate was relatively ineffective. All these analogues were effective in megaloblastic marrows from folate deficient patients. Formyltetrahydrofolates also enhanced dU utilization by normal human marrows whereas methyltetrahydrofolate reduced its use. In terms of the methylfolate trap hypothesis, the expectation that cobalamin-deficient marrows would be able to use tetrahydrofolate normally was not realized.

Topics: Anemia, Megaloblastic; Anemia, Pernicious; Bone Marrow; Bone Marrow Cells; Deoxyuridine; Folic Acid; Formyltetrahydrofolates; Humans; Hydroxocobalamin; Methylation; Tetrahydrofolates

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

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