MUTATIONS IN MUT METHYLMALONIC ACIDEMIA - CLINICAL AND ENZYMATIC CORRELATIONS

Mut methylmalonic acidemia is caused by mutations in the MUT locus enc oding the enzyme methylmalonyl CoA mutase. Genotypic and phenotypic va riability in this disease has been studied exten sively by biochemical and somatic cell genetic techniques, by molecular cloning, and by gen e transfer. Mutations have been identified that cause classic mut(o) p henotypes in which there is no detectable enzymatic activity, mut(-) p henotypes in which there is residual cobalamin dependent activity, as well as a subset within both mut(o) and mut(-) phenotypes that exhibit interallelic complementation. These mutations illustrate the position , structure, and function of critical domains within this cobalamin-bi nding enzyme and provide new insights into the biochemical and clinica l consequences of enzyme deficiency. (C) 1997 Wiley-Liss, Inc.