Clinical, biochemical, and mutational spectrum of peroxisomal acyl-coenzyme A oxidase deficiency

Hum Mutat. 2007 Sep;28(9):904-12. doi: 10.1002/humu.20535.


Peroxisomal acyl-coenzyme A (acyl-CoA) oxidase deficiency is an autosomal recessive inborn error of peroxisomal fatty acid oxidation due to a deficiency of straight-chain acyl-CoA oxidase (SCOX). The biochemical hallmark of this disorder is the accumulation of very long-chain fatty acids. Although some case reports and small series of patients have been published, a comprehensive overview of the clinical, biochemical, and mutational spectrum of this disorder is still lacking. For this reason, we report clinical information for a cohort of 22 patients with peroxisomal acyl-CoA oxidase deficiency and the results from biochemical and mutation analyses in fibroblasts of the patients. No clear genotype-phenotype correlation was observed. An intriguing mutation in the alternatively-spliced transcript encoding the isoform SCOX-exon 3II in a patient with normal expression of the transcript encoding the isoform SCOX-exon 3I, prompted us to characterize these two isoforms of human SCOX. The recombinant SCOX-exon 3I displayed activity toward medium-chain fatty acyl-CoAs and was not active with very long-chain fatty acyl-CoAs. In contrast, recombinant SCOX-exon 3II was capable of oxidizing a broad range of substrates, including very long-chain fatty acyl-CoAs. These results explain why this patient with a mutation in exon 3II of the ACOX1 gene, but with normal expression of exon 3I, was indistinguishable from other patients with peroxisomal acyl-CoA oxidase deficiency with respect to his clinical presentation and the biochemical abnormalities in his fibroblasts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl-CoA Oxidase
  • Amino Acid Sequence
  • Biomarkers / analysis
  • Cells, Cultured
  • Cohort Studies
  • DNA Mutational Analysis
  • Fatty Acids / analysis
  • Fibroblasts / chemistry
  • Fibroblasts / enzymology
  • Genotype
  • Humans
  • Isoenzymes / genetics
  • Lipid Metabolism, Inborn Errors / genetics*
  • Lipid Metabolism, Inborn Errors / pathology*
  • Molecular Sequence Data
  • Mutation*
  • Oxidoreductases / genetics*
  • Oxidoreductases / metabolism*
  • Peroxisomal Disorders / genetics*
  • Peroxisomal Disorders / pathology*
  • Phenotype
  • Sequence Homology, Amino Acid


  • Biomarkers
  • Fatty Acids
  • Isoenzymes
  • Oxidoreductases
  • peroxisomal acyl-CoA oxidase
  • Acyl-CoA Oxidase