摘要
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 E1αcomponent.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 E1αgene 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 E1αgene is a mutation leading to pyruvate dehydrogenase complex deficiency in this family.
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 E1αcomponent.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 E1αgene 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 E1αgene is a mutation leading to pyruvate dehydrogenase complex deficiency in this family.
