脑型肝豆状核变性患者临床特征及基因突变分析  

Analysis of clinical characteristics and gene mutation of 56 patients with cerebral wilson disease

作　　者：黄叶青[1] 古玉梅 刁胜朋[1] 刘爱群[1] 洪铭范[1] HUANG Yeqing;GU Yumei;DIAN Shengpeng;LIU Aiqun;HONG Mingfan(The 1^(st)Affiliated Hospital of Guangdong Pharmaceutical University,Guangzhou 518000,China;不详)

机构地区：[1]广东药科大学附属第一医院,广东广州518000

出　　处：《现代医院》2021年第4期646-648,共3页Modern Hospitals

基　　金：广东省中医药局面上项目基金资助(20180320230014)。

摘　　要：目的分析脑型肝豆状核变性病人的临床特点和基因突变的特点。方法收集2010年1月-2020年3月我院56例脑型肝豆状核变性患者,分析发病年龄、病程、临床表现特点、血象、肝功能、腹部B超、颅脑磁共振、ATB7B基因变异特点。结果56例脑型肝豆状核变性病人中发病年龄11~20岁34例(60.7%),病程1~3年35例(62.5%);临床表现以震颤起病16例(28.6%),构音障碍起病24例(42.8%),伴有精神、性格障碍者5例(8.9%);56例(100%)24 h尿铜>100μg;45例(80.35%)血清铜蓝蛋白低于0.2 g/L;眼科裂隙灯下可见角膜K-F环阳性56例(100%),血细胞减少5例(8.9%),转氨酶升高12例(21.4%),50例(89.2%)腹部彩超结果均有异常,41例(73.2%)头颅磁共振有异常;42例(75%)患者检测出致病变异位点,表现为复合杂合突变或纯合突变,14例(25%)患者仅检测到单个突变位点。所有致病变异中,Arg778 Leu在本研究人群中等位频率最高,占25.9%(29/112),其中3例为纯合突变;其次为Ile1148Thr(15/112)、Gly943Asp(6/112)、2304 dup C(5/112)、Pro992Leu(4/112),等位频率分别为13.4%、5.3%、4.5%、3.6%。结论脑型肝豆状核变性患者临床表现多样,临床上对于类似患者要完善铜蓝蛋白、24 h尿铜、角膜K-F环、腹部彩超、颅脑磁共振等相关检查,基因检测有助于提高早期诊断率。Objective To analyze the clinical features and gene mutation of patients with cerebral Wilson disease.Methods 56 patients with cerebral Wilson disease in our hospital from January 2010 to March 2020 were collected,and the characteristics of age of onset,course of disease,clinical features,blood image,liver function,abdominal B-ultrasound,brain magnetic resonance,ATB7 B gene variation were analyzed.Results Among the 56 patients,34(60.7%)were aged 11-20,and 35(62.5%)were aged 1-3.The clinical manifestations were tremor in 16 patients(28.6%),articulation disorder in 24 patients(42.8%),and mental and personality disorders in 5 patients(8.9%).56 cases(100%)24 h urinary copper>100 ug;The serum level of copper cyanin was lower than 0.2 g/L in 45 cases(80.35%).There were 56 cases(100%)with positive corneal K-F ring,5 cases(8.9%)with hemopenia,12 cases(21.4%)with elevated aminotransferase,50 cases(89.2%)with abnormal abdominal color doppler ultrasonography,and 41 cases(73.2%)with abnormal cranial MAGNETIC resonance.Pathogenetic mutation sites were detected in 42 patients(75%),presenting as complex heterozygous or homozygous mutations,and only a single mutation site was detected in 14 patients(25%).Among all the pathogenic variants,Arg778 Leu had the highest medium frequency in the study population,accounting for 25.9%(29/112),among which 3 cases were homozygous mutations.Ile1148 Thr(15/112),Gly943 Asp(6/112),2304 dupC(5/112)and Pro992 Leu(4/112)were followed by Ile1148 Thr,Gly943 Asp(6/112),with the allelic frequencies of 13.4%,5.3%,4.5%and 3.6%respectively.Conclusion There are various clinical manifestations in patients with cerebral Wilson disease.In clinical practice,it is necessary to improve related examinations such as copper cyanin,24 h urinary copper,corneal K-F ring,abdominal color doppler ultrasound,and brain magnetic resonance imaging for similar patients.Gene detection is helpful to improve the early diagnosis rate.

关 键 词：肝豆状核变性 脑型 临床特点 基因突变 

分 类 号：R742[医药卫生—神经病学与精神病学]