| Pyruvate dehydrogenase deficiency: identification of a novel mutation in the PDHA1 gene which responds to amino acid supplementation. | |
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MedLine Citation:
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PMID: 18398624 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. Conclusion: 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. |
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Authors:
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Maria João Silva; Ana Pinheiro; Filomena Eusébio; Ana Gaspar; Isabel Tavares de Almeida; Isabel Rivera |
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Publication Detail:
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Type: Case Reports; Journal Article Date: 2008-04-09 |
Journal Detail:
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Title: European journal of pediatrics Volume: 168 ISSN: 1432-1076 ISO Abbreviation: Eur. J. Pediatr. Publication Date: 2009 Jan |
Date Detail:
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Created Date: 2008-11-26 Completed Date: 2009-04-28 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7603873 Medline TA: Eur J Pediatr Country: Germany |
Other Details:
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Languages: eng Pagination: 17-22 Citation Subset: IM |
Affiliation:
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Unidade de Biologia Molecular e Biopatologia Experimental, Centro de Patogénese Molecular, Faculdade de Farmácia da Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisboa, Portugal. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Arginine
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therapeutic use* Aspartic Acid / therapeutic use* Blotting, Western Child DNA Mutational Analysis Gene Expression / genetics Humans Male Point Mutation / genetics* Polymerase Chain Reaction Polymorphism, Single-Stranded Conformational / genetics Pyruvate Dehydrogenase (Lipoamide) / genetics* Pyruvate Dehydrogenase Complex Deficiency Disease / drug therapy*, genetics* |
| Chemical | |
Reg. No./Substance:
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56-84-8/Aspartic Acid; 74-79-3/Arginine; 7675-83-4/arginine aspartate; EC 1.2.4.1/Pyruvate Dehydrogenase (Lipoamide); EC 1.2.4.1/pyruvate dehydrogenase E1alpha subunit |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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