Document Detail

Pyruvate dehydrogenase deficiency: identification of a novel mutation in the PDHA1 gene which responds to amino acid supplementation.
MedLine Citation:
PMID:  18398624     Owner:  NLM     Status:  MEDLINE    
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.
Maria João Silva; Ana Pinheiro; Filomena Eusébio; Ana Gaspar; Isabel Tavares de Almeida; Isabel Rivera
Related Documents :
21565494 - Enzymatic enrichment of polyunsaturated fatty acids using novel lipase preparations mod...
18596034 - His-311 and arg-559 are key residues involved in fatty acid oxygenation in pathogen-ind...
15963714 - Strain improvement for tannase production from co-culture of aspergillus foetidus and r...
6449654 - Induction of lambdoid prophages by amino acid deprivation: differential inducibility; r...
14572664 - Osgstu3 and osgtu4, encoding tau class glutathione s-transferases, are heavy metal- and...
572624 - Effect of removal of carbohydrate residues upon the half life and in vivo biological ac...
Publication Detail:
Type:  Case Reports; Journal Article     Date:  2008-04-09
Journal Detail:
Title:  European journal of pediatrics     Volume:  168     ISSN:  1432-1076     ISO Abbreviation:  Eur. J. Pediatr.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2008-11-26     Completed Date:  2009-04-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7603873     Medline TA:  Eur J Pediatr     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  17-22     Citation Subset:  IM    
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.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Arginine / therapeutic use*
Aspartic Acid / therapeutic use*
Blotting, Western
DNA Mutational Analysis
Gene Expression / genetics
Point Mutation / genetics*
Polymerase Chain Reaction
Polymorphism, Single-Stranded Conformational / genetics
Pyruvate Dehydrogenase (Lipoamide) / genetics*
Pyruvate Dehydrogenase Complex Deficiency Disease / drug therapy*,  genetics*
Reg. No./Substance:
56-84-8/Aspartic Acid; 74-79-3/Arginine; 7675-83-4/arginine aspartate; EC Dehydrogenase (Lipoamide); EC dehydrogenase E1alpha subunit

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Umbilical artery blood S100beta protein: a tool for the early identification of neonatal hypoxic-isc...
Next Document:  Differential diagnosis of oocysts of Hammondia-like organisms of dogs and cats by PCR-RFLP analysis ...