Methylmalonic Aciduria: Metabolic Block Localization and Vitamin B12 Dependency
Leon E. Rosenberg 1,
Anne-Charlotte Lilljeqvist 1, and
Yujen Edward Hsla 1
1 Departments of Pediatrics and Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510
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.
