Mutations in mut methylmalonic acidemia: clinical and enzymatic correlations

Mut methylmalonic acidemia is caused by mutations in the MUT locus encoding the enzyme methylmalonyl CoA mutase. Genotypic and phenotypic variability in this disease has been studied extensively by biochemical and somatic cell genetic techniques, by molecular cloning, and by gene transfer. Mutations have been identified that cause classic mut(o) phenotypes in which there is no detectable enzymatic activity, mut- phenotypes 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-binding enzyme and provide new insights into the biochemical and clinical consequences of enzyme deficiency.