ACOX2 deficiency: A disorder of bile acid synthesis with transaminase elevation, liver fibrosis, ataxia, and cognitive impairment
ACOX2 deficiency: A disorder of bile acid synthesis with transaminase elevation, liver fibrosis, ataxia, and cognitive impairment
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DOI：
10.1073/pnas.1613228113
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发表时间：
2016-10-04
影响因子：
11.1
通讯作者：
Lifton, Richard P.
中科院分区：
文献类型：
--
作者：
Vilarinho, Silvia;Sari, Sinan;Lifton, Richard P.
酰基辅酶 A 氧化酶 2 (ACOX2) 编码支链酰基辅酶 A 氧化酶，这是一种过氧化物酶体酶，据信参与支链脂肪酸和胆汁酸中间体的代谢。以前没有描述过这种酶的缺乏。我们报告一名 8 岁男性，患有间歇性转氨酶水平升高、肝纤维化、轻度共济失调和认知障碍。外显子组测序揭示了 ACOX2 中先前未识别的纯合提前终止突变 (p.Y69*)。免疫组织化学证实患者肝脏中不存在 ACOX2 表达，生化分析显示 ACOX2 上游中间胆汁酸显着升高。这些发现定义了一种可能可治疗的由 ACOX2 缺乏引起的胆汁酸生物合成先天性缺陷。
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.