累代遗传的肝豆状核变性的临床与基因诊断分析  

Clinical and genetic diagnosis of hepatolenticular degeneration occurring in two consecutive generations

作　　者：刘力生 方明娟 年娜 赵雯 童广安 王佳炜 胡文彬 LIU Lisheng;FANG Mingjuan;NIAN Na(Institute of Neurology,Anhui University of Chinese Medicine,Hefei 230061,China)

机构地区：[1]安徽中医药大学神经病学研究所,安徽合肥230061 [2]安徽中医药大学神经病学研究所附属医院神经内科,安徽合肥230061

出　　处：《中风与神经疾病杂志》2024年第1期52-57,共6页Journal of Apoplexy and Nervous Diseases

基　　金：国家自然科学基金(81473535)。

摘　　要：目的总结分析累代遗传的肝豆状核变性(HLD)的临床与基因诊断思路。方法通过对2017年6月—2023年7月我科收治的3例HLD患者的现病史、既往史、家族史的收集调查,并对其可能患病的一级亲属进行肝功能、血清铜蓝蛋白(CP)、基础24 h尿铜(尿Cu)、角膜K-F环(KFR)、腹部彩超及ATP7B基因检测、分析。结果3个家系的先证者的父母或子女中共有2例转氨酶升高,3例CP减低和尿Cu升高,1例患有脂肪肝,ATP7B基因均为复合杂合突变,KFR均阴性。明确了3个累代遗传的HLD家系,并发现了一个新的致病突变。结论单纯以CP、KFR或腹部彩超等筛查症状前期HLD存在较大局限性,尿Cu检测敏感性良好,基因检测可进一步提高诊断的准确性。由于HLD人群携带率较高,HLD的累代遗传现象值得重视。Objective To investigate the ideas for the clinical and genetic diagnosis of hepatolenticular degeneration(HLD)occurring in two consecutive generations.Methods The information on history of present illness,past history,and family history were collected from three patients with HLD who were admitted to our department from June 2017 to July 2023,and their first-degree relatives who might have this disease were examined in terms of liver function,serum ceruloplasmin(CP),basal 24-hour urinary copper excretion(urinary Cu),Kayser-Fleischer ring(KFR)of the cornea,abdominal ultrasound,and ATP7B gene testing.Results Among the parents or children of the probands in these three families,two were found to have elevated serum aminotransferases,three had a reduction in CP and an increase in urinary Cu,and 1 had fatty liver;all of them had compound heterozygous mutations in the ATP7B gene,and all tested negative for KFR.This study identified three families with HLD occurring in two consecutive generations and found a new pathogenic mutation.Conclusion CP,KFR,or abdominal ultrasound has certain limitations in screening pre-symptomatic HLD;urinary Cu test has a good sensitivity,and genetic testing can further improve the accuracy of diagnosis.Due to the high carrying rate of ATP7B pathogenic mutations in the population with HLD,HLD occurring in two consecutive generations should be taken seriously in clinical practice.

关 键 词：肝豆状核变性 累代遗传 ATP7B 诊断分析 

分 类 号：R742.4[医药卫生—神经病学与精神病学]