Pyruvate dehydrogenase complex (PDHc) deficiency is an X-linked inborn error of mitochondrial energy metabolism. Defects in the PDH complex are an important cause of primary lactic acidosis. The phenotype of patients with a PDH complex deficiency include an early neonatal presentation with severe lactic acidosis and early death, a progressive disease with mental retardation and neurological complications, or intermittent ataxia. Recurrent acute proximal muscle weakness of upper and lower extremities has also been reported as the presenting feature in one affected individual. Dysmorphic features including hypertelorism, a long narrow prominent forehead, long philtrum, thin lips, sparse eyelashes, cranial asymmetry, small hands and feet, short inferior limbs, and hypospadias have also been described. Antenatally, neurodevelopmental lesions, craniofacial dysmorphisms, and fetal akinesia deformation sequence/ arthrogryposis multiplex congenita may be present.
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, 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.