Methylmalonic Aciduria: Metabolic Block Localization and Vitamin B 12 Dependency

Abstract

Methylmalonic aciduria is an inborn error of metabolism characterized by neonatal or infantile ketoacidosis. Leukocytes isolated from the peripheral blood of a 1-year-old child with this disorder converted negligible quantities of propionate-3-C¹⁴ to carbon dioxide, but oxidized succinate-1,4-C¹⁴ normally, an indication of a block in the conversion of propionate to succinate. Parenteral administration of vitamin B¹⁸ resulted in a reduction in methylmalonic acid excretion and an increase in propionate oxidation by leukocytes in vitro. The results suggest a mutation of methylmalonyl-CoA isomerase, a vitamin B₁₂, dependent enzyme which converts methylmalonyl-CoA to succinyl-CoA, and provide the first demonstration of vitamin B₁₂ "dependency" in man.