Defect in the X-lipoyl-containing component of the pyruvate dehydrogenase complex in a patient with a neonatal lactic acidemia

Studies of human pyruvate dehydrogenase (PDH) deficiency have shown that defects in the E1 component are not common, with only a small number of defects associated specifically with the E3, E2, and component X subunits. We report here clinical, enzymatic, and immune studies of the PDH complex (PDHc) in a girl presenting with a primary defect in the component X. The patient, born from nonconsanguineous parents, presented with severe neonatal lactic acidosis, minor facial dysmorphia, and complete corpus callosum agenesis. The metabolic profile revealed marked hyperlactatemia and hyperpyruvic acidemia, with a normal lactate/pyruvate ratio and no detectable ketosis or hyperammonemia. The activity of total PDHc in cultured skin fibroblasts and in fresh mononuclear cells was markedly decreased by about 80% as compared with the controls and with the parents.