A family with pyruvate dehydrogenase complex deficiency due to a novel C>T substitution at nucleotide position 407 in exon 4 of the X-linked Epsilon1alpha gene.
Eur J Pediatr
; 164(2): 99-103, 2005 Feb.
Article
en En
| MEDLINE
| ID: mdl-15558317
ABSTRACT
UNLABELLED The pyruvate dehydrogenase complex (PDHc; McKusick 312170), localised in the mitochondrial matrix, is a multienzyme complex which converts pyruvate to acetyl-CoA. A deficiency of PDHc leads to inadequate removal of pyruvate and lactate resulting in lactic acidaemia and insufficient energy production. The major cause of PDHc deficiency is a defect in the E1alpha component. The gene of this component is localised to Xp22.1. We describe two brothers with a relatively mild clinical phenotype of PDHc deficiency. Onset of disease was associated with muscle weakness and swallowing difficulties in both. At follow-up, the older brother developed encephalopathic features consistent with Leigh syndrome. Lactate to pyruvate ratios were low, consistent with a PDHc deficiency which was confirmed by measurements of PDHc activity in thrombocytes. A 407C>T change in exon 4 of the E1alpha gene was found in both brothers and their mother. This substitution predicts a replacement of a conserved alanine at position 136 by valine. CONCLUSION:
Due to the X-linked inheritance pattern combined with the overall results of clinical investigations, molecular genetic findings and a corresponding functional deficiency of the gene product we believe that this substitution in the pyruvate dehydrogenase E1alpha gene is a mutation leading to pyruvate dehydrogenase complex deficiency in this family.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedad por Deficiencia del Complejo Piruvato Deshidrogenasa
/
Sustitución de Aminoácidos
/
Piruvato Deshidrogenasa (Lipoamida)
Tipo de estudio:
Prognostic_studies
Límite:
Child, preschool
/
Humans
/
Infant
/
Male
Idioma:
En
Revista:
Eur J Pediatr
Año:
2005
Tipo del documento:
Article
País de afiliación:
Suecia