DEFECT IN 5′-DEOXYADENOSYLCOBALAMIN SYNTHESIZING ENZYME IN METHYLMALONICACIDEMIA

Inherited methylmalonicacidemia (MM-emia) due to deficient activity of methylmalonyl-CoA mutase may be caused by an abnormal mutase apoenzyme or by reduced holoenzyme activity secondary to impaired synthesis of the mutase-requiring coenzyme, 5'-deoxyadenosylcobalamin (Ado-Cbl). We studied Ado-Cbl synthesis in 5 fibroblast lines from unrelated patients who have MM-emia due to defective cobalamin (vitamin B12) metabolism. Their whole cells in culture fail to synthesize Ado-Cbl but make normal amounts of the other cobalamin coenzyme, methylcobalamin.