Pyruvate dehydrogenase complex (PDHc) deficiency due to mutations in the PDHA1 gene is an X-linked inborn error of mitochondrial energy metabolism. Defects in the PDH complex are an important cause of primary lactic acidosis, and clinical symptoms of patients with a PDH complex deficiency vary considerably, ranging from intermittent ataxia to a progressive disease with mental retardation and neurological complications to an early neonatal presentation with severe lactic acidosis and early death. Dysmorphic features including hypertelorism, a long narrow prominent forehead, long philtrum, thin lips, scarce eyelashes, cranial asymmetry, small hands and feet; short inferior limbs and hypospadias have also been described. Equal numbers of affected males and females have been identified. Males typically present with severe neonatal lactic acidosis while the presentation in females is more variable and is dependent upon the pattern of X-inactivation. Females have been reported with a severe phenotype that includes microcephaly, spastic quadriplegia, severe epilepsy and cortical/subcortical atrophy.