ACOX2 deficiency: A disorder of bile acid synthesis with transaminase elevation, liver fibrosis, ataxia, and cognitive impairment.

TitleACOX2 deficiency: A disorder of bile acid synthesis with transaminase elevation, liver fibrosis, ataxia, and cognitive impairment.
Publication TypeJournal Article
Year of Publication2016
AuthorsVilarinho, S, Sari, S, Mazzacuva, F, Bilguvar, K, Esendagli-Yilmaz, G, Jain, D, Akyol, G, Dalgiç, B, Günel, M, Clayton, PT, Lifton, RP
JournalProc Natl Acad Sci U S A
Volume113
Issue40
Pagination11289-11293
Date Published2016 Oct 04
ISSN1091-6490
KeywordsAtaxia, Bile Acids and Salts, Child, Cognitive Dysfunction, Homozygote, Humans, Infant, Infant, Newborn, Liver, Liver Cirrhosis, Loss of Function Mutation, Male, Mutation, Oxidation-Reduction, Oxidoreductases, Transaminases
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.
DOI10.1073/pnas.1613228113
Alternate JournalProc Natl Acad Sci U S A
PubMed ID27647924
PubMed Central IDPMC5056113
Grant ListP30 DK034989 / DK / NIDDK NIH HHS / United States
U54 HG006504 / HG / NHGRI NIH HHS / United States
UL1 TR001863 / TR / NCATS NIH HHS / United States