vitamin-b-12 and Diseases-in-Twins

The methylmalonic aciduria is an organic acidemia, inherited as autosomic recessive trait, caused by a deficiency of the methylmalonyl-CoA mutase, or by defects in the biosynthesis of the cofactor adenosylcobalamin. Regarding the enzymatic defect, there are two forms: mut(o) with no detectable enzymatic activity and mut(-) with reduced activity. Its clinical presentation may vary from a severe neonatal form with acidosis and death, up to a progressive chronic form. Here we describe the case of a four year-old boy, with diagnosis of methylmalonyl-CoA mutase deficiency type mut(-) with an acute presentation. Molecular analysis of MUT gene identified two mutations c.607G>A (G203R) and c.2080C>T (R694W), later confirmed in the parents. The aim of this report is to highlight the importance of including the organic acid analysis in urine among the first line exams in acutely and severely ill children with undefined etiology. The definitive diagnosis is important because it may allow a specific treatment and a favorable evolution to prevent the secuelae.

Topics: Acidosis; Amino Acid Substitution; Child, Preschool; Coma; Diet, Protein-Restricted; Diseases in Twins; Fertilization in Vitro; Genes, Recessive; Humans; Male; Metabolism, Inborn Errors; Methylmalonic Acid; Methylmalonyl-CoA Mutase; Mutation, Missense; Point Mutation; Twins, Dizygotic; Vitamin B 12; Vomiting

The extent of genetic influence on plasma homocysteine, a risk factor for ischaemic heart disease, is uncertain. Many association studies have investigated common polymorphisms and their role in hyperhomocysteinaemia, but only the thermolabile variant of methylene tetrahydrofolate reductase (MTHFR) has shown an association (small but robust).. To estimate the heritability of plasma homocysteine and the contributions of well-studied common SNPs in the three main candidate genes in the homocysteine methylation pathway.. Twin study.. We studied 216 monozygotic and 790 dizygotic pairs of twins; all were women. Blood was collected after overnight fasting for measurement of homocysteine, folate, vitamin B12, and extraction of DNA. Heritability was estimated by structural modelling, including correction for known environmental influences, particularly serum folate. The frequency of a common coding SNP in MTHFR and methionine synthase (MTR), and two coding SNPs in methionine synthase reductase (MTRR) were measured in dizygotic twins by ABI 7700 Sequence Detection, and the contribution of each to homocysteine variance was determined.. The heritability of homocysteine was 57% (95%CI 51-63%). The highest contribution to homocysteine was serum folate, accounting for 10.13% of variance. This was twice the total genetic contribution of 4.56%, and only the C1763T SNP of MTRR showed significant association with homocysteine.. Homocysteine has one of the highest heritabilities of common risk factors for ischaemic heart disease. This is not accounted for by the commonly studied SNPs in MTHFR, MTR and MTRR.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Adolescent; Adult; Aged; Diseases in Twins; Female; Folic Acid; Homocysteine; Humans; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Myocardial Ischemia; Polymorphism, Single Nucleotide; Surveys and Questionnaires; Vitamin B 12

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

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

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

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

The tendency towards metabolic acidosis developing during simple infections lead to the detection of hyperglycinemia which was shown to be caused by the rare inborn error of metabolism, which was shown to be a methylmalonic acidemia, in identical twins. Under a protein restricted diet and vitamin-B12-injections once a week, all clinical symptoms disappeared so that vitamin-B12-dependency became evident. Under this therapeutic regimen methylmalonic aciduria was well under control.

Topics: Acidosis; Diseases in Twins; Glycine; Humans; Infant; Malonates; Metabolism, Inborn Errors; Methylmalonic Acid; Vitamin B 12

Topics: Anemia, Pernicious; Antibodies; Blood Cell Count; Bone Marrow Examination; Diseases in Twins; Folic Acid; Gastric Juice; Gastroscopy; Hematocrit; Humans; Intrinsic Factor; Male; Malonates; Microscopy, Electron; Middle Aged; Schilling Test; Vitamin B 12

Topics: Aged; Anemia, Pernicious; Diseases in Twins; Female; Humans; Iron; Vitamin B 12