ACOX2 deficiency: A disorder of bile acid synthesis with transaminase elevation, liver fibrosis, ataxia, and cognitive impairment
- PMID: 27647924
- PMCID: PMC5056113
- DOI: 10.1073/pnas.1613228113
ACOX2 deficiency: A disorder of bile acid synthesis with transaminase elevation, liver fibrosis, ataxia, and cognitive impairment
Abstract
Acyl CoA Oxidase 2 (ACOX2) encodes branched-chain acyl-CoA oxidase, a peroxisomal enzyme believed to be involved in the metabolism of branched-chain fatty acids and bile acid intermediates. Deficiency of this enzyme has not been described previously. We report an 8-y-old male with intermittently elevated transaminase levels, liver fibrosis, mild ataxia, and cognitive impairment. Exome sequencing revealed a previously unidentified homozygous premature termination mutation (p.Y69*) in ACOX2 Immunohistochemistry confirmed the absence of ACOX2 expression in the patient's liver, and biochemical analysis showed marked elevation of intermediate bile acids upstream of ACOX2. These findings define a potentially treatable inborn error of bile acid biosynthesis caused by ACOX2 deficiency.
Keywords: bile acid metabolism; branched-chain acyl-CoA oxidase; idiopathic liver disease; peroxisomal disorder; whole-exome sequencing.
Conflict of interest statement
Dr. Lifton and Dr. Valle were coauthors (neither of them first or last author) on a 40-author review of progress in Mendelian genetics published in 2015. This paper came about because they are independently funded grantees from NIH for discovery of new Mendelian loci. They have never been research collaborators.
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Comment in
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ACOX2 deficiency in primary malignant cardiac tumors.Proc Natl Acad Sci U S A. 2017 May 2;114(18):E3590-E3591. doi: 10.1073/pnas.1701212114. Epub 2017 Apr 11. Proc Natl Acad Sci U S A. 2017. PMID: 28400508 Free PMC article. No abstract available.
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