title: 2-Methylbutyryl-coenzyme A dehydrogenase deficiency: a new inborn error of L-isoleucine metabolism.
abstract: 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.
authors.affiliation: Department of Molecular and Medical Genetics, Oregon Health Sciences University, Portland 97201, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Gibson
authors.forename: T G
authors.initials: TG
authors.lastname: Burlingame
authors.forename: B
authors.initials: B
authors.lastname: Hogema
authors.forename: C
authors.initials: C
authors.lastname: Jakobs
authors.forename: R B
authors.initials: RB
authors.lastname: Schutgens
authors.forename: D
authors.initials: D
authors.lastname: Millington
authors.forename: C R
authors.initials: CR
authors.lastname: Roe
authors.forename: D S
authors.initials: DS
authors.lastname: Roe
authors.forename: L
authors.initials: L
authors.lastname: Sweetman
authors.forename: R D
authors.initials: RD
authors.lastname: Steiner
authors.forename: L
authors.initials: L
authors.lastname: Linck
authors.forename: P
authors.initials: P
authors.lastname: Pohowalla
authors.forename: M
authors.initials: M
authors.lastname: Sacks
authors.forename: D
authors.initials: D
authors.lastname: Kiss
authors.forename: P
authors.initials: P
authors.lastname: Rinaldo
authors.forename: J
authors.initials: J
authors.lastname: Vockley
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000097:blood / Q000175:diagnosis*; D001483:Base Sequence; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D017931:DNA Primers; D018076:DNA, Complementary; D005260:Female; D006801:Humans; D007223:Infant; D007532:Isoleucine / Q000378:metabolism*; D008297:Male; D010088:Oxidoreductases / Q000097:blood* / Q000235:genetics; D044925:Oxidoreductases Acting on CH-CH Group Donors; D011247:Pregnancy; D011296:Prenatal Diagnosis
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; C116917:acylcarnitine; D007532:Isoleucine; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; C038808:2-methylacyl-CoA dehydrogenase; D002331:Carnitine