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

In a case of dihydrolipoyl dehydrogenase deficiency, there was not only an elevation of lactate and alpha-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 alloisoleucine 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, alpha-ketoglutarate dehydrogenase, and branched chain keto acid dehydrogenases.