2-Methylbutyryl-coenzyme A dehydrogenase deficiency: a new inborn error of L-isoleucine metabolism.
Journal Article (Journal Article)
An 4-mo-old male was found to have an isolated increase in 2-methylbutyrylglycine (2-MBG) and 2-methylbutyrylcamitine (2-MBC) in physiologic fluids. In vitro oxidation studies in cultured fibroblasts using 13C- and 14C-labeled branched chain amino acids indicated an isolated block in 2-methylbutyryl-CoA dehydrogenase (2-MBCDase). Western blotting revealed absence of 2-MBCDase protein in fibroblast extracts; DNA sequencing identified a single 778 C>T substitution in the 2-MBCDase coding region (778 C>T), substituting phenylalanine for leucine at amino acid 222 (L222F) and absence of enzyme activity for the 2-MBCDase protein expressed in Escherichia coli. Prenatal diagnosis in a subsequent pregnancy suggested an affected female fetus, supporting an autosomal recessive mode of inheritance. These data confirm the first documented case of isolated 2-MBCDase deficiency in humans.
- Gibson, KM; Burlingame, TG; Hogema, B; Jakobs, C; Schutgens, RB; Millington, D; Roe, CR; Roe, DS; Sweetman, L; Steiner, RD; Linck, L; Pohowalla, P; Sacks, M; Kiss, D; Rinaldo, P; Vockley, J
- June 2000
Volume / Issue
- 47 / 6
Start / End Page
- 830 - 833
International Standard Serial Number (ISSN)
Digital Object Identifier (DOI)
- United States