VITAMIN B12 DEPENDENT METHYLMALONICACIDURIA - DEFECTIVE B12 METABOLISM IN CULTURED FIBROBLASTS

Intact fibroblasts from children with vitamin B12 dependent methylmalonicaciduria failed to isomerize methylmalonate to succinate, and contained less than 10 percent of the normal amount of 5′-deoxyadenosylcobalamin (B12 coenzyme) when grown in a standard culture medium. Both metabolic abnormalities disappeared, however, when a B12-supplemented growth medium was employed.These findings, plus the demonstration that methylmalonyl-CoA mutase apoenzyme activity in whole cell homogenates from these mutant lines was not impaired, indicate that B12 dependent methylmalonicaciduria is caused by a defect in the biosynthesis or metabolism of 5′-deoxyadenosylcobalamin. To our knowledge, such a defect in human vitamin metabolism has not been demonstrated previously in tissue culture. © 1969.