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

Pediatr Res. 2000 Jun;47(6):830-3. doi: 10.1203/00006450-200006000-00025.


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.

Publication types

  • Case Reports

MeSH terms

  • Amino Acid Metabolism, Inborn Errors / blood
  • Amino Acid Metabolism, Inborn Errors / diagnosis*
  • Base Sequence
  • Carnitine / analogs & derivatives
  • Carnitine / blood
  • DNA Primers
  • DNA, Complementary
  • Female
  • Humans
  • Infant
  • Isoleucine / metabolism*
  • Male
  • Oxidoreductases / blood*
  • Oxidoreductases / genetics
  • Oxidoreductases Acting on CH-CH Group Donors*
  • Pregnancy
  • Prenatal Diagnosis


  • DNA Primers
  • DNA, Complementary
  • acylcarnitine
  • Isoleucine
  • Oxidoreductases
  • Oxidoreductases Acting on CH-CH Group Donors
  • 2-methylacyl-CoA dehydrogenase
  • Carnitine