Pyruvate dehydrogenase complex deficiency: four neurological phenotypes with differing pathogenesis
Article first published online: 1 DEC 2009
© The Authors. Journal compilation © Mac Keith Press 2009
Developmental Medicine & Child Neurology
Volume 52, Issue 2, pages e1–e9, February 2010
How to Cite
BARNERIAS, C., SAUDUBRAY, J.-M., TOUATI, G., DE LONLAY, P., DULAC, O., PONSOT, G., MARSAC, C., BRIVET, M. and DESGUERRE, I. (2010), Pyruvate dehydrogenase complex deficiency: four neurological phenotypes with differing pathogenesis. Developmental Medicine & Child Neurology, 52: e1–e9. doi: 10.1111/j.1469-8749.2009.03541.x
- Issue published online: 15 JAN 2010
- Article first published online: 1 DEC 2009
- PUBLICATION DATA Accepted for publication 18th August 2009. Published online.
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.