Pyruvate dehydrogenase complex deficiency: four neurological phenotypes with differing pathogenesis

Dev Med Child Neurol. 2010 Feb;52(2):e1-9. doi: 10.1111/j.1469-8749.2009.03541.x. Epub 2009 Dec 1.


Aim: To describe the phenotype and genotype of pyruvate dehydrogenase complex (PDHc) deficiency.

Method: Twenty-two participants with enzymologically and genetically confirmed PDHc deficiency were analysed for clinical and imaging features over a 15-year period.

Results: Four groups were identified: (1) those with neonatal encephalopathy with lactic acidosis (one male, four females; diagnosis at birth); (2) those with non-progressive infantile encephalopathy (three males, three females; age at diagnosis 2-9mo); (3) those with Leigh syndrome (eight males; age at diagnosis 1-13mo); and (4) those with relapsing ataxia (three males; 18-30mo). Seventeen mutations involved PDHA1 (a hotspot was identified in exons 6, 7, and 8 in seven males with Leigh syndrome or recurrent ataxia). Mutations in the PDHX gene (five cases) were correlated with non-progressive encephalopathy and long-term survival in four cases.

Interpretation: Two types of neurological involvement were identified. Abnormal prenatal brain development resulted in severe non-progressive encephalopathy with callosal agenesis, gyration anomalies, microcephaly with intrauterine growth retardation, or dysmorphia in both males and females (12 cases). Acute energy failure in infant life produced basal ganglia lesions with paroxysmal dystonia, neuropathic ataxia due to axonal transport dysfunction, or epilepsy only in males (11 cases). The ketogenic diet improved only paroxysmal dysfunction, providing an additional argument in favour of paroxysmal energy failure.

MeSH terms

  • Adolescent
  • Brain / pathology
  • Female
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging / methods
  • Male
  • Motor Skills Disorders / etiology
  • Mutation / genetics*
  • Nervous System Diseases / drug therapy
  • Nervous System Diseases / etiology
  • Nervous System Diseases / genetics*
  • Nervous System Diseases / pathology*
  • Peripheral Nervous System / pathology
  • Phenotype*
  • Pyruvate Dehydrogenase Complex / genetics*
  • Pyruvate Dehydrogenase Complex Deficiency Disease / drug therapy
  • Pyruvate Dehydrogenase Complex Deficiency Disease / genetics*
  • Pyruvate Dehydrogenase Complex Deficiency Disease / pathology*
  • Retrospective Studies
  • Thiamine / therapeutic use
  • Vitamin B Complex / therapeutic use


  • PDHX protein, human
  • Pyruvate Dehydrogenase Complex
  • Vitamin B Complex
  • Thiamine