A 6-month-old female infant with hypotonia and keto and lactic acidosis was diagnosed with lipoamide dehydrogenase (E3) deficiency. This enzyme is a component of the pyruvate, alpha-ketoglutarate, and branched chain alpha-ketoacid dehydrogenase complexes. At the time of diagnosis her plasma contained elevated branched chain amino acids, alanine, alloisoleucine, ketones, pyruvate, and lactate, and her urine contained elevated branched chain ketoacids and lactate. By neuroimaging she was found to have Leigh subacute necrotizing encephalomyelopathy. Modest branched-chain amino acid restriction led to the disappearance of alloisoleucine and normalization of her branched chain amino acid values, while institution of a high fat diet precipitated hypoglycemia and acidosis. A trial of lipoic acid led to a transient modest improvement in her lactic acidemia. Use of dichloroacetate to activate the pyruvate dehydrogenase complex led to a significant decline in lactate levels, but this was also transient. The patient had significant growth failure despite a high carbohydrate, high calorie diet, yet remained clinically well until 28 months of age when she developed acute acidosis and brainstem dysfunction and died.