METHYLMALONIC ACIDURIA - METABOLIC BLOCK LOCALIZATION AND VITAMIN B12 DEPENDENCY

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 B12 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."