Effect of Lipoic Acid in a Patient with Defective Activity of Pyruvate Dehydrogenase, 2-Oxoglutarate Dehydrogenase, and Branched- Chain Keto Acid Dehydrogenase

Abstract

ABSTRACT: Lactic acidosis and accumulation of 3-hydroxybutyrate and other citric acid cycle intermediates were found in an infant with a lethal syndrome of metabolic acidosis and renal tubular acidosis. Nevertheless, the patient was relatively well for 4 mo of life. The activity of the pyruvate dehydrogenase complex, 2-oxoglutarate dehydrogenase, and branched-chain keto acid dehydrogenase were all reduced to levels 9 to 29% of control. In contrast, the activity of lipoamide dehydrogenase was normal. The conversion of 1-¹⁴C-leucine and 1-¹⁴C-valine to ¹⁴CO₂ and of U-L-¹⁴C-valine to its major metabolic product 3-hydroxyisobutyric acid by fibroblasts derived from the patient was less than 5% of control. Cultivation of the patient's fibroblasts in medium enriched with lipoic acid markedly improved these in vitro conversions of leucine and valine.

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