Source:http://linkedlifedata.com/resource/pubmed/id/16752391
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
7
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pubmed:dateCreated |
2006-6-26
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pubmed:abstractText |
Methylmalonic aciduria (MMA-uria) is an autosomal recessive inborn error of amino acid metabolism, involving valine, threonine, isoleucine, and methionine. This organic aciduria may present in the neonatal period with life-threatening metabolic acidosis, hyperammonemia, feeding difficulties, pancytopenia, and coma. Most affected patients have mutations in the methylmalonyl-coenzyme A (methylmalonyl-CoA) mutase gene. Mildly affected patients may present in childhood with failure to thrive and recurrent attacks of metabolic acidosis. Both a higher residual activity of methylmalonyl-CoA mutase as well as the vitamin B12-responsive defects (cblA and cblB) may form the basis of the mild disorder. A few patients with moderate MMA-uria are known in whom no defect could be identified. Here we present a 16-year-old female patient with persisting moderate MMA-uria (approximately 50 mmol/mol creatinine). She was born to consanguineous Caucasian parents. Her fibroblast mutase activity was normal and no effect of vitamin B12 supplementation could be established. Reduced incorporation of 14C-propionate into macromolecules suggested a defect in the propionate-to-succinate pathway. We found a homozygous nonsense mutation (c.139C>T) in the methylmalonyl-CoA epimerase gene (MCEE), resulting in an early terminating signal (p.R47X). Both parents were heterozygous for this mutation; they were found to excrete normal amounts of methylmalonic acid (MMA). This is the first report of methylmalonyl-CoA epimerase deficiency, thereby unequivocally demonstrating the biochemical role of this enzyme in human metabolism.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Codon, Nonsense,
http://linkedlifedata.com/resource/pubmed/chemical/Methylmalonic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Racemases and Epimerases,
http://linkedlifedata.com/resource/pubmed/chemical/methylmalonyl-coenzyme A racemase
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1098-1004
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pubmed:author | |
pubmed:copyrightInfo |
Copyright 2006 Wiley-Liss, Inc.
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pubmed:issnType |
Electronic
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pubmed:volume |
27
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
640-3
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:16752391-Amino Acid Metabolism, Inborn Errors,
pubmed-meshheading:16752391-Child, Preschool,
pubmed-meshheading:16752391-Codon, Nonsense,
pubmed-meshheading:16752391-Consanguinity,
pubmed-meshheading:16752391-DNA Mutational Analysis,
pubmed-meshheading:16752391-Female,
pubmed-meshheading:16752391-Homozygote,
pubmed-meshheading:16752391-Humans,
pubmed-meshheading:16752391-Methylmalonic Acid,
pubmed-meshheading:16752391-Racemases and Epimerases
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pubmed:year |
2006
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pubmed:articleTitle |
A homozygous nonsense mutation in the methylmalonyl-CoA epimerase gene (MCEE) results in mild methylmalonic aciduria.
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pubmed:affiliation |
Laboratory of Genetic Metabolic Diseases and Department of Clinical Genetics/Pediatrics/Pediatric Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
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pubmed:publicationType |
Journal Article,
Case Reports
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