极长链酰基辅酶A脱氢酶缺乏症1个家系的报道并文献复习  

Very-long chain acyl-coA dehydrogenase deficiency:report of a Chinese pedigree and a literature review

作　　者：蔡世岩 杨俊逸[2] 王诗宇 陈红 赵文静 周笑颜 章印红 Cai Shiyan;Yang Junyi;Wang Shiyu;Chen Hong;Zhao Wenjing;Zhou Xiaoyan;Zhang Yinhong(Department of Pediatrics,the First Hospital of Kunming,Kunming,Yunnan 650011,China;Clinical Laboratory,Kunming Children′s Hospital,Kunming,Yunnan 650100,China;School of Medicine,Kunming University of Science and Technology,Kunming,Yunnan 650500,China;Department of Medical Genetics,National Health Commission Key Laboratory of Preconception Birth Health in Western China,Yunnan Provincial Key Laboratory for Birth Defects and Genetic Diseases,the First People′s Hospital of Yunnan Province,Affiliated Hospital of Kunming University of Science and Technology,Kunming,Yunnan 650032,China)

机构地区：[1]昆明市第一人民医院儿科,昆明650011 [2]昆明市儿童医院检验科,昆明650100 [3]昆明理工大学医学院,昆明650500 [4]昆明理工大学附属医院、云南省第一人民医院医学遗传科,国家卫生健康委西部孕前优生重点实验室,云南省出生缺陷与遗传病研究重点实验室,昆明650032

出　　处：《中华医学遗传学杂志》2024年第1期59-66,共8页Chinese Journal of Medical Genetics

基　　金：云南省出生缺陷和遗传病研究重点实验室开放课题(2020ZDKFKT001);云南省生殖妇产疾病临床医学中心(zx2019-01-01)开放课题(2022LCZXKF-SZ02);昆医联合专项-青年博士项目(202001AY070001-156);云南省第一人民医院博士科研基金(KHBS-2020-018)。

摘　　要：目的探讨中国籍极长链酰基辅酶A脱氢酶缺乏症(VLCADD)患儿的临床分型与基因型和预后之间的相关性。方法对本院2019年2月接诊的1个VLCADD家系进行回顾性总结,分析其发病特点、诊治过程及预后,并对相关文献进行回顾。结果患儿,男,1岁,主要表现为频繁发作的呕吐、低血糖、肝功能及心肌酶异常。足跟血串联质谱筛查显示C14、C14:1、C16:1、C16:2、C18和C14/C8明显升高,基因检测发现患儿ACADVL基因存在c.664G>A(p.G222R)和c.1345G>A(p.E449K)复合杂合变异,分别来源于父亲和母亲,患儿被确诊为VLCADD,临床分型为心肌病型。患儿于入院2周后死亡。结合文献报道,共收集60例中国籍VLCADD患儿的资料,其临床分型以心肌病型和肝病型为主,占比达73.3%(43/60);基因变异组合类型与临床分型有一定的相关性,心肌病型患儿多携带2个功能丧失突变(LOF);心肌病型预后最差,死亡率高达76.9%(20/26)。C14:1作为诊断VLCADD的敏感指标,无法用于临床分型和预后评估。c.1349G>A(p.R450H)变异频次最高,占10.8%(13/120)。结论VLCADD的临床分型与预后高度相关。LOF变异在临床表现严重的患儿中更为常见。c.1349G>A(p.R450H)变异可能是中国人群中最常见的变异,早期筛查和诊断可以极大改善患儿的预后。Objective To explore the correlation between clinical classification and genotype and prognosis among Chinese children with Very-long chain acyl-CoA dehydrogenase deficiency(VLCADD).Methods A Chinese pedigree affected with VLCADD admitted at the First People′s Hospital of Yunnan Province in February 2019 was selected as the study subject.The characteristics of disease onset,diagnosis and treatment and prognosis were retrospectively analyzed.Relevant literature was also systematically searched and reviewed.Results The proband,a 1-year-old boy,had the clinical manifestations of frequently vomiting,hypoglycemia,abnormal liver function and myocardial enzymes.Tandem mass spectrometry screening showed significantly elevated C14,C14:1,C16:1,C16:2,C18 and C14/C8.Genetic testing revealed that he has harbored compound heterozygous variants of the ACADVL gene,namely c.664G>A(p.G222R)and c.1345G>A(p.E449K),which were respectively derived from his father and mother.The child was diagnosed with VLCADD cardiomyopathy type and deceased 2 weeks later.Literature review has identified 60 Chinese children with VLCADD.The clinical classifications were mainly cardiomyopathy type and liver disease type,which accounted for 73.3%(43/60).The combination of ACADVL gene variants were correlated with the clinical classifications of VLCAD.Children with one or two loss-of-function(LOF)mutations showed more severe clinical manifestation and a higher mortality.Cardiomyopathy type had the poorest prognosis,with a mortality rate of 76.9%(20/26).C14:1 may be used as an indicator for the diagnosis of VLCADD,but cannot be used for clinical subtyping and prognosis evaluation.The c.1349G>A(p.R450H)variant had the highest frequency among the Chinese patients,accounting for 10.8%(13/120).Conclusion The clinical classifications of VLCADD are strongly correlated with the prognosis,and LOF mutations are more common in those with severe clinical manifestations.c.1349G>A(p.R450H)may be the most common variant among the Chinese patients,and early screening a

关 键 词：极长链酰基辅酶A脱氢酶 ACADVL基因 极长链脂肪酸 线粒体脂肪酸β氧化 

分 类 号：R725.9[医药卫生—儿科]