A defect in branched-chain amino acid metabolism in a patient with congenital lactic acidosis due to dihydrolipoyl dehydrogenase deficiency

Abstract

In a case of dihydrolipoyl dehydrogenase deficiency, there was not only an elevation of lactate and α-ketoglutarate but also of branched chain amino acids. The levels of branched- chain amino acids varied from the normal range to three times the upper limit of normal during the patient’s lifetime, and allo- isoleucine was detectable at all times. Examination of postmortem tissues revealed that the activity of branched-chain keto acid dehydrogenases was between zero and 10% of that in control tissues. It is suggested that the multiple defects seen in oxidative decarboxylation in this patient is the consequence of a single genetic deletion of an enzyme common to pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and branched- chain keto acid dehydrogenases. Speculation: The dihydrolipoyl dehydrogenase component of pyruvate, α- ketoglutarate, and branched-chain keto acid dehydrogenases is genetically and biochemically a single entity. © 1978 International Pediatric Research Foundation, Inc.