Isolated isobutyryl-CoA dehydrogenase deficiency: An unrecognized defect in human valine metabolism

Charles R. Roe, Stephen D. Cederbaum, Diane S. Roe, Rebecca Mardach, Alvaro Galindo, Lawrence Sweetman

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


A 2-year-old female was well until 12 months of age when she was found to be anemic and had dilated cardiomyopathy. Total plasma carnitine was 6 μM and acylcarnitine analysis while receiving carnitine supplement revealed an increase in the four-carbon species. Urine organic acids were normal. In vitro analysis of the mitochondrial pathways for beta oxidation, and leucine, valine, and isoleucine metabolism was performed in fibroblasts using stable isotope-labeled precursors to these pathways followed by acylcarnitine analysis by tandem mass spectrometry. 16-2H3-palmitate was metabolized normally down to the level of butyryl-CoA thus excluding SCAD deficiency. 13C6-leucine and 13C6-isoleucine were also metabolized normally. 13C5-valine incubation revealed a significant increase in 13C4- isobutyrylcarnitine without any incorporation into propionylcarnitine as is observed normally. These same precursors were also evaluated in fibroblasts with proven ETF-QO deficiency in which acyl-CoA dehydrogenase deficiencies in each of these pathways was clearly identified. These results indicate that in the human, there is an isobutyryl-CoA dehydrogenase which exists as a separate enzyme serving only the valine pathway in addition to the 2-methyl branched-chain dehydrogenase which serves both the valine and the isoleucine pathways in both rat and human.

Original languageEnglish (US)
Pages (from-to)264-271
Number of pages8
JournalMolecular genetics and metabolism
Issue number4
StatePublished - Dec 1998
Externally publishedYes


  • Acylcarnitine
  • Branched-chain amino acids
  • Cardiomyopathy
  • Carnitine
  • Dehydrogenase
  • Isobutyryl-CoA
  • Valine

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology


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