Methylmalonic aciduria without vitamin B12 deficiency in an adult sibship.

Two brothers 62 and 70 years old, without evidence of vitamin B12 lack, excreted 12 to 115 mg of methylmalonic acid daily (normal, less than 9 mg per day). Neither had anemia or hepatic dysfunction, and serum vitamin B12 concentrations ranged from 369 to 800 pg per milliliter. The propositus, the younger brother, continued to excrete excessive methylmalonate, 103 to 115 mg per day, after 2000 mug of parenterally administered vitamin B12 at the fifth and 11th months of study. Leukocyte activities of the cobalamin-linked enzyme methylmalonyl coenzyme A mutase were respectively reduced in the propositus and his brother, to 0.04 and 0.11 nmoles of 3-(14)-C Ls methylmalonyl coenzyme A metabolized per hour per milligram of leukocyte protein (normal, 0.286 +/- 0.079 [S.D.]). These activities were not enhanced by 2 mug of 5'-deoxyadenosylcobalamin added to the assays. A heritable benign form of adult methylmalonic aciduria rather than vitamin B12 lack best explains these findings.