Abstract
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 31, prompted us to characterize these two isoforms of human SCOX. The recombinant SCOX-exon 31 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 311 of the ACOX1 gene, but with normal expression of exon 31, was indistinguishable from other patients with peroxisomal acyl-CoA oxidase deficiency with respect to his clinical presentation and the biochemical abnormalities in his fibroblasts.
Original language | English (US) |
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Pages (from-to) | 904-912 |
Number of pages | 9 |
Journal | Human mutation |
Volume | 28 |
Issue number | 9 |
DOIs | |
State | Published - Sep 2007 |
Keywords
- ACOX
- Acyl-CoA oxidase
- Beta-oxidation
- Peroxisome
- SCOX
- Straight-chain acyl-CoA oxidase
- Very long-chain fatty acids
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)