Rare Diseases Symptoms Automatic Extraction

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 E1alpha on immunoblotting analysis. Molecular studies showed a novel and "de novo" mutation in the PDHA1 gene, R253G. 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 PDHA1 mutations with mild phenotypes.our results encourage the use of amino acid supplementation to overcome the metabolic/biochemical changes induced by PDHA1 gene specific mutations associated with mild PDHc phenotypes.

Diseases presenting "low pdhc activity with absence of e1alpha on immunoblotting analysis" symptom

  • pyruvate dehydrogenase deficiency

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