title: [Pyruvate dehydrogenase deficit associated to the C515T mutation in exon 6 of the E1alpha gene].
abstract: BACKGROUND
  Pyruvate dehydrogenase (PDH) deficiency constitutes the most frequent metabolic origin of congenital lactic acidosis and is also responsible for a less usual form, found exclusively in females, which leads to a dysmorphic syndrome accompanied by severe cerebral malformations. The most common defect affects fraction E1alpha (gene Xp22.1-22.2).
  
  
  OBJECTIVE
  To report the case of a young female with PDH deficiency, dysmorphic syndrome, cerebral deformations and an unidentified mutation in the corresponding gene.
  
  
  METHODS
  An 8-month-old female with microcephaly, a narrow forehead, nasal hypoplasia, anteverted nostrils, thin lips, axial hypotonia, epileptic seizures and an umbilical hernia. Magnetic resonance imaging of the brain revealed intense supra- and infratentorial cortico-subcortical atrophy, ventricular dilatation and agenesis of the corpus callosum. Lactic and pyruvic acid concentrations were high both in blood and in cerebrospinal fluid (CSF), and the level of alanine was high in CSF. Muscular histology results were normal. PDH complex activity in fibroblasts and in muscle tissue, as well as that of the mitochondrial respiratory chain complexes in muscle homogenate, were found to be normal. A molecular genetic study of the gene for PDHE1alpha, both in formed elements in the blood and in fibroblasts, showed a C > T change in nucleotide 515 (C515T) of exon 6, which causes a P172L change in the protein. A study of 108 controls ruled out the possibility of a polymorphism. The parents did not have the mutation.
  
  
  CONCLUSIONS
  The C515T mutation of exon 6 of the gene for PDH E1alpha is described. Normal activity of the PDH complex in fibroblasts and in muscle tissue does not exclude this condition.
authors.affiliation: Departamendo de Pediatría, Servicio de Neuropediatría, Hospital Clinico Universitario, Santiago de Compostela, 15706 Santiago de Compostela, Espana.
authors.forename: O
authors.initials: O
authors.lastname: Blanco-Barca
authors.forename: C
authors.initials: C
authors.lastname: Gomez-Lado
authors.forename: E
authors.initials: E
authors.lastname: Rodrigo-Saez
authors.forename: C
authors.initials: C
authors.lastname: Curros-Novos
authors.forename: P
authors.initials: P
authors.lastname: Briones-Godino
authors.forename: J
authors.initials: J
authors.lastname: Eiris-Punal
authors.forename: M
authors.initials: M
authors.lastname: Castro-Gago
mesh_terms: D001921:Brain / Q000002:abnormalities; D041321:Chromosomes, Human, X; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007223:Infant; D018482:Muscle, Skeletal; D010641:Phenotype; D017354:Point Mutation; D030481:Pyruvate Dehydrogenase (Lipoamide) / Q000235:genetics* / Q000378:metabolism; D015325:Pyruvate Dehydrogenase Complex Deficiency Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology
chemical_list: D030481:Pyruvate Dehydrogenase (Lipoamide); C065640:pyruvate dehydrogenase E1alpha subunit