过氧化物酶体酰基辅酶A氧化酶缺乏症一例并文献复习  

Peroxisomal acyl-CoA oxidase deficiency: one case report and literature review

作　　者：尤桦菁 田杨 李洵桦[1] 李小晶 裴中[1] YOU Hua-jing;TIAN Yang;LI Xun-hua;LI Xiao-jing;PEI Zhong(Department of Neurology,The First Affiliated Hospital,Sun Yat-sen University,Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases,National Key Clinical Department and Key Discipline of Neurology,Guangzhou 510080,Guangdong,China;Department of Neurology,Guangzhou Women and Children's Medical Center,Guangzhou 510623,Guangdong,China)

机构地区：[1]中山大学附属第一医院神经科广东省重大神经疾病诊治研究重点实验室,国家临床重点专科和国家重点学科,广州510080 [2]广东省广州市妇女儿童医疗中心神经内科,510623

出　　处：《中国现代神经疾病杂志》2021年第4期281-288,共8页Chinese Journal of Contemporary Neurology and Neurosurgery

基　　金：国家重点研发计划项目(项目编号:2017YFA0105104);国家自然科学基金资助项目(项目编号:81873751);国家自然科学基金资助项目(项目编号:82071255);华南神经疾病早期干预及功能修复研究国际合作基地(项目编号:2015B050501003);广东省神经系统重大疾病诊治工程项目;广东省神经系统重大疾病诊治转化医学创新平台项目;广东省神经系统疾病临床医学研究项目。

摘　　要：目的首次报道1例国内ACOX1基因突变致过氧化物酶体酰基辅酶A氧化酶缺乏症患儿,结合文献综述其临床特征。方法与结果男性患儿,出生时肌张力偏低、生长发育迟缓并出现抽搐发作1次,3岁时出现神经功能退化并快速进展至无法独坐、独自站立和行走,语言表达能力倒退;体格检查可见特殊面容、锥体束征及小脑损害。头部MRI显示双侧脑干和小脑对称性脱髓鞘改变;血清极长链脂肪酸(VLCFAs)水平升高。全外显子组测序,患儿存在ACOX1基因c.1589A> G(p.His530Arg)纯合突变,其父母均携带ACOX1基因c.1589A> G(p.His530Arg)杂合突变,但无临床症状,符合家系共分离现象;根据美国医学遗传学和基因组学会(ACMG)指南,该变异为可能致病突变。患儿最终诊断为过氧化物酶体酰基辅酶A氧化酶缺乏症。结论对于新生儿期发病的肌张力低下、癫发作和生长发育迟缓,若头部MRI显示小脑、脑干等对称性异常信号,应高度警惕过氧化物酶体病,阳性家族史、VLCFAs水平升高和基因检测可明确诊断。Objective To report a case of peroxisomal acyl-CoA oxidase(ACOX1) deficiency,which was caused by an unreported mutation of ACOX1 gene, and review its clinical characteristics.M ethods and Results The male child patient suffered from neonatal hypotonia,developmental retardation and epilepsy seizure once since neonatal period. Neurodegeneration appeared at the age of 3 and developed rapidly to difficulty of sitting, standing and walking independently and retrogressive language expression ability. Physical examination showed special face, pyramidal tract sign and cerebellar signs. Cranial MRI revealed symmetric demyelinating lesions in bilateral brain stem and cerebellum along with increased serum very-long-chain fatty acids(VLCFAs). Whole exome sequencing revealed c. 1589 A > G(p. His530 Arg)homozygous mutation in ACOX1 gene. His parents carried the same heterozygous mutation without symptoms and this phenomenon was in accord with co-segregation. According to the guidelines of American College of Medical Genetics and Genomics(ACMG), we considered this new variation to be possibly pathogenic variation. Finally, the patient was diagnosed as ACOX1 deficiency.Conclusions As for patients who suffer from hypotonia, epilepsy seizure and growth retardation since neonatal period, they should be altered to ACOX1 deficiency if cranial MRI shows symmetrical abnormal foci in cerebellum and brain stem. Positive family history, increased VLCFAs level, and gene detection would be beneficial to definite diagnosis.

关 键 词：过氧化物酶体类 酰基CoA氧化酶 基因 突变 

分 类 号：R725.8[医药卫生—儿科]