Inherited propionyl-Coa carboxylase deficiency in "ketotic hyperglycinemia"

Abstract

Cultured fibroblasts from a young girl with ketotic hyperglycinemia were unable to oxidize propionate-(14)C to (14)CO(2), but oxidized methylmalonate-(14)C and succinate-(14)C normally. This block in propionate catabolism was shown to result from a lack of propionyl-CoA carboxylase activity. The carboxylase deficiency was not due to the presence of an intracellular inhibitor and it was not corrected by biotin, a known cofactor for the enzyme. Both of her parents' fibroblasts had approximately 50% of normal propionyl-CoA carboxylase activity. These results demonstrate that ketotic hyperglycinemia and propionicacidemia are the same disease, caused by a mutation of the propionyl-CoA carboxylase apoenzyme, which is inherited as an autosomal recessive trait. This enzymatic localization provides an explanation for the remarkable clinical and chemical similarity between ketotic hyperglycinemia and methylmalonicaciduria and offers a potential means of antenatal detection of this disorder.