2-Methylbutyryl-coenzyme a dehydrogenase deficiency: A new inborn error of L-isoleucine metabolism

K. Michael Gibson, Terry G. Burlingame, Boris Hogema, Cornelis Jakobs, Ruud B.H. Schutgens, David Millington, Charles R. Roe, Diane S. Roe, Lawrence Sweetman, Robert D. Steiner, Leesa Linck, Parhawa Pohowalla, Martine Sacks, Doreen Kiss, Piero Rinaldo, Jerry Vockley

Research output: Contribution to journalArticlepeer-review

84 Scopus citations


An 4-mo-old male was found to have an isolated increase in 2- methylbutyrylglycine (2-MBG) and 2-methylbutyrylcarnitine (2MBC) 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 ferns, supporting an autosomal recessive mode of inheritance. These data confirm the first documented case of isolated 2-MBCDase deficiency in humans.

Original languageEnglish (US)
Pages (from-to)830-833
Number of pages4
JournalPediatric Research
Issue number6
StatePublished - Jun 2000
Externally publishedYes

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health


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