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Molecular characterization of methylmalonate semialdehyde dehydrogenase deficiency
Author(s) -
Chambliss K. L.,
Gray R. G. F.,
Rylance G.,
Pollitt R. J.,
Gibson K. M.
Publication year - 2000
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1023/a:1005616315087
Subject(s) - transversion , methylmalonic acid , biochemistry , catabolism , isoleucine , chemistry , alanine , metabolite , inborn error of metabolism , amino acid , maple syrup urine disease , valine , arginine , gene , genetics , biology , metabolism , mutation , leucine , homocysteine
Three patients have been reported with (putative) methylmalonic semialdehyde dehydrogenase (MMSDH) deficiency. The urine metabolic pattern was strikingly different in all, including β‐alanine, 3‐hydroxypropionic acid, both isomers of 3‐amino‐ and 3‐hydroxyisobutyric acids in one and 3‐hydroxyisobutyric and lactic acids in a second, and mild methylmalonic aciduria in a third patient. In an effort to clarify these disparate metabolite patterns, we completed the cDNA structure, and characterized the genomic structure of human MMSDH gene in order to undertake molecular analysis. Only the first patient had alterations in the MMSDH coding region, revealing homozygosity for a 1336G>A transversion, which leads to substitution of arginine for highly conserved glycine at amino acid 446. No abnormalities of the MMSDH cDNA were detected in the other patients. These data provide the first molecular characterization of an inborn error of metabolism specific to the L‐valine catabolic pathway.