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[Pyruvate dehydrogenase deficit associated to the C515T mutation in exon 6 of the E1alpha gene]

O Blanco-Barca1, C Gomez-Lado, E Rodrigo-Saez

  • 1Departamendo de Pediatría, Servicio de Neuropediatría, Hospital Clinico Universitario, Santiago de Compostela, 15706 Santiago de Compostela, Espana.

Revista De Neurologia
|September 19, 2006
PubMed

Insights

Pyruvate dehydrogenase deficiency in a female infant caused severe brain malformations. A novel C515T mutation in the PDHE1alpha gene was identified, even with normal enzyme activity in tissues.

Area of Science:

  • Biochemistry
  • Genetics
  • Neurology

Background:

  • Pyruvate dehydrogenase (PDH) deficiency is a primary cause of congenital lactic acidosis.
  • A rare subtype affects females, presenting with dysmorphic syndrome and severe cerebral malformations, often linked to the PDHE1alpha gene.

Observation:

  • An 8-month-old female infant exhibited microcephaly, dysmorphic features, hypotonia, and seizures.
  • Brain MRI revealed significant atrophy, ventricular dilatation, and agenesis of the corpus callosum.
  • Elevated lactic and pyruvic acid levels were noted in blood and CSF, alongside high CSF alanine.

Findings:

  • Despite normal PDH complex and mitochondrial respiratory chain activity in fibroblasts and muscle, a novel C515T mutation in exon 6 of the PDHE1alpha gene was detected.
  • This mutation resulted in a P172L amino acid change, confirmed not to be a common polymorphism.

Implications:

  • This case highlights a novel mutation causing PDH deficiency with severe neurological consequences.
  • Normal PDH enzyme activity in accessible tissues does not rule out the condition, emphasizing the importance of genetic testing.
Abstract

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