- Vitamin B12-responsive methylmalonicaciduria
- An inherited metabolic (biochemical) disease that, unless effectively treated, causes young children to become mentally retarded. The defect in some (but not all) of these children has to do with an inability to use the vitamin B12 they ingest. If these children are given very large supplements of vitamin B12, they can overcome, in part, the metabolic defect and do better. The clinical spectrum of methylmalonicaciduria is wide, ranging from a benign condition to a fatal neonatal disease. In its severe form, methylmalonicaciduria is characterized by profound metabolic acidosis (excess acidity), developmental retardation (slowed infant development), and a characteristic biochemical triad of abnormalities (in technical terms: methylmalonicaciduria, long chain ketonuria, and intermittent hyperglycinemia.) Some but not all patients with methylmalonicaciduria respond to vitamin B12. An enzyme called methylmalonyl-CoA mutase is defective in the disease. This enzyme requires the presence of adenosylcobalamin, a form of vitamin B12. The metabolic block in methylmalonicacidemia occurs at methylmalonyl-CoA mutase and can be caused by defects in the mutase itself, or in the synthesis of the mutase cofactor adenosylcobalamin. There is also an extraordinarily benign form of methylmalonicaciduria due to deficiency of methylmalonyl-CoA mutase. The gene for this enzyme (methylmalonyl-CoA mutase) has been mapped to chromosome 6 in region 6p21.1-p12 and has been cloned. More than 30 different mutations in the gene have been identified, each causing methylmalonicaciduria.
Medical dictionary. 2011.