Pyruvate dehydrogenase deficiency: identification of a novel mutation in the PDHA1 gene which responds to amino acid supplementation.

[pyruvate dehydrogenase deficiency]

The pyruvate dehydrogenase complex (PDHc ) is an intramitochondrial multienzyme system , which plays a key role in aerobic glucose metabolism by catalysing the oxidative decarboxylation of pyruvate to acetyl-CoA . Genetic defects in the PDHc lead to lactic acidemia and neurological abnormalities . In the majority of the cases , the defect appears to reside in the E (1 )alpha subunit , the first catalytic component of the complex . The report is on a 6 -year -old Portuguese boy with mild neurological involvement and low PDHc activity with absence of E 1 alpha on immunoblotting analysis . Molecular studies showed a novel and "de novo " mutation in the PDHA 1 gene , R 253 G . Treatment with arginine aspartate showed complete clinical and biochemical recovery . We hypothesise that arginine aspartate acts as a chemical or pharmacological chaperone , and suggest amino acid supplementation as a possible therapy in PDHA 1 mutations with mild phenotypes .our results encourage the use of amino acid supplementation to overcome the metabolic /biochemical changes induced by PDHA 1 gene specific mutations associated with mild PDHc phenotypes .

Diseases
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Diseases presenting "mutation in the pdha1 gene" symptom

pyruvate dehydrogenase deficiency

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