| Autor: |
Tulinius, M´r, Darin, Niklas, Wiklund, Lars-Martin, Holmberg, Eva, Eriksson, Jan Erik, Lissens, Willy, De Meirleir, Linda, Holme, Elisabeth, Tulinius, Már |
| Předmět: |
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| Zdroj: |
European Journal of Pediatrics; Feb2005, Vol. 164 Issue 2, p99-103, 5p, 2 Diagrams, 3 Charts |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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