cblC: advances in defining the MMACHC mutation spectrum.

摘要

In 1975 Mahoney et al. (Proc Nail Acad Sci USA 72:2799-803) named those mutants with deficient accumulation of both 5'-deoxyadenosylcobalamin (AdoCbl) and metbylcobalamin (MeCbl) "cblC mutants". Due to a defect in synthesis of two different cofactors, the cblC group exhibits a pleiotropic deficiency of both methylmalonyl CoA mutase activity and N~5-mefhyltetrabydrofo-late: homocysteine methyltransferase activity. The cblC defect is the most common disorder of intracellular vitamin B_(12) (cobalamin or Cbl) metabolism. Patients with this disorder suffer from combined homocystinuria and methylmalonic aciduria, resulting in hemato-logic, neurologic, metabolic, ophthalmologic, and dermatologic manifestations. The identification of MMACHC, the gene on chromosome 1 responsible for cblC, was accomplished in 2006 by Lerner-Ellis et al. (Nat Genet 38:93-100). The function of MMACHC is not known; it may act as an intracellular cobalamin trafficking chaperone that carries out targeted delivery of cobalamin to and from other cobalamin-related proteins.