A male child died at 7 months of age with progressive neurologic deterioration and persistent metabolic acidosis. Investigations during life showed this child to have elevated blood pyruvate, lactate, and α-ketoglutarate as well as elevation of branched chain amino acids and occasional hypoglycemia. Co-factor therapy using either thiamine-HCI (2 g/kg/24 hr) or thiamine tetrahydrofurfuryl disulfide had no measurable effect on the clinical or biochemical status of the patient. Tissue taken postmortem showed normal levels of key gluconeogenic enzymes but a deficiency in the activity of pyruvate dehydrogenase in all tissues tested (liver, brain, kidney, skeletal muscle, and heart). Examination of the individual activities of the pyruvate dehydrogenase complex showed pyruvate decarboxylase (E 1) to be normal in liver and other tissues. Dihydrolipoyl dehydrogenase (E 3), on the other hand, was deficient in all tissues tested. α-Ketoglutarate dehydrogenase complex, which depends on E 3 for its total activity, was also deficient in all tissues tested. The absence of this enzyme is discussed in relation to the clinical and biochemical status of the patient.

Speculation: Congenital lactic acidosis due to a severe defect in the pyruvate dehydrogenase complex for the first time has been shown to be due to the absence of the E 3 enzyme of the pyruvate dehydrogenase complex, dihydrolipoyl dehydrogenase. The survival of this infant for 6 weeks of life without hospitalization is suggestive of a reliance on glycolytic rather than oxidative metabolism in the early neonatal period.