Methylmalonic Aciduria without Vitamin B12Deficiency in an Adult Sibship

Abstract

Two brothers 62 and 70 years old, without evidence of vitamin B₁₂ lack, excreted 12 to 115 mg of methylmalonic acid daily (normal, 12 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 μg 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 μg of 5′-deoxyadenosylcobalamin added to the assays. A heritable benign form of adult methylmalonic aciduria rather than vitamin B₁₂ lack best explains these findings. (N Engl J Med 295:310–313, 1976)