Defective metabolism of vitamin B12 in fibroblasts from children with methylmalonicaciduria

Abstract Fibroblasts from a patient with B 12 responsive methylmalonicaciduria and from a second patient with methylmalonicaciduria plus abnormal sulfur amino acid metabolism were examined for their ability to accumulate the two B 12 coenzymes, deoxyadenosyl-B 12 ∗ and methyl-B 12 , and for N 5 -methyltetrahydrofolate homocysteine methyltransferase activity. Cells from the first patient accumulated very little deoxyadenosyl-B 12 but accumulated methyl-B 12 normally. His cells had normal methyltransferase activity when assayed with and without added methyl-B 12 coenzyme. In contrast, cells from the second patient accumulated neither coenzyme. Methyltransferase activity was very low when assayed without added methyl-B 12 but increased markedly when coenzyme was added. We conclude that both patients have primary defects in vitamin B 12 metabolism and that these defects are biochemically distinct.