以肝病为首发表现的儿童肝豆状核变性临床、病理及基因突变特征研究  

Clinical, pathological and gene mutation features of Wilson's disease in children with liver disease as initial manifestation

作　　者：朱世殊[1] 董漪[1] 徐志强[1] 甘雨[1] 陈大为[1] 王丽旻[1] 王福川[1] 钟彦伟[1] 姜君[2] 张鸿飞[1] 

机构地区：[1]解放军第三〇二医院青少年肝病诊疗与研究中心,北京100039 [2]中国科学院北京基因组研究所,北京100005

出　　处：《传染病信息》2013年第5期272-275,共4页Infectious Disease Information

摘　　要：目的总结以肝病为首发表现的儿童肝豆状核变性（Wilson’sdisease，WD）的临床、病理及基陶突变特征，以提高对这类疾病的早期诊断水平。方法回顾性分析2005年1月--2013年1月我院收治的以肝病为首发表现的317例WD患儿（年龄11月龄～16岁，中位数9．0岁）的临床、病理及基因诊断资料。结果以肝病为首发表现的患儿如果病情未进展到晚期肝病，确诊WD前均无临床症状，25．9％的患者被误诊。31．9％的患儿存在贫血，18．6％的患儿合并肾损伤，90．9％的患儿血清铜蓝蛋白水平异常。≤7岁组Kayser-F1eiseher（K—F）环及头颅MRI检查阳性率分别为20．0％和O％，〉7岁组阳性率分别为79．1％和14．9％。肝脏病理主要病变表现为不同程度的慢性肝炎样改变，44．5％的患儿有不同程度的脂肪变性，35．4％有严重肝纤维化，14．0％有活动性肝硬化，82．3％铜染色阳性。39．O％的患儿出现ATP7B基因778号密码子突变，34．1％出现复合纯合突变，4．9％出现Thr935Met号密码子突变。结论对于任何年龄儿童出现不明原因的转氨酶增高和肝硬化，排除病毒性肝炎后首先应考虑WD的可能。即使血清铜蓝蛋白水平正常，K—F环和头颅MRI检查阴性也不能完全排除WD，须进一步通过患儿24h尿铜测定、青霉胺激发试验、肝脏病理学检查及ATP7B基因检测进行综合判断。Objective To summarize the clinical, pathological and gene mutation features of Wilson＇s disease （WD） in child- ren with liver disease as initial manifestation, so as to improve the early diagnosis of such WD patients. Methods A total of 317 child WD patients with liver disease as initial manifestation, who were admitted to our hospital from Jan. 2005 to Jan. 2013, aged from 11 months old to 16 years old, with the median age of 9.0 years old, were enrolled in the study. The clinical, pathological and gene mutation characteristics of the patients were retrospectively analyzed. Results The child patients with liver disease as initial manifestation, whose disease had not progressed to end-stage of liver disease, had no clinical symptoms before they were diagnosed with WD. Of them, 25.9% were misdiagnosed. Anemia and renal injury occurred in 31.9% and 18.6% of the patients, respectively. Serum ceruloplasmin level was abnormal in 90.9% of the patients. The positive rates of Kayser-Fleischer （K-F） rings and skull MRI were 20.0% and 0%, respectively, among children under the age of 7 years old, while 79.1% and 14.9%, respectively, among chil- dren aged 7-16 years old. The major pathological changes that occurred within the liver were chronic hepatitis at different degrees, 44.5% with fatty degeneration, 35.4% severe fibrosis, 14.0% active cirrhosis, and 82.3% copper staining positive. Mutations in codon 778 of ATPTB gene were seen in 39.0% of the patients, compound homozygous mutations in 34.1%, and mutations in codon Thr935Met in 4.9%. Conclusions For child patients with unexplained elevated transaminase and cirrhosis, WD should be firstly considered after excluding viral hepatitis. Even if serum ceruloplasmin level is normal, and K-F rings and skull MRI are negative, 24-hour urinary copper test, penicillamine test, liver biopsy and ATP7B gene test are needed to make a comprehensive diagnosis of WD.

关 键 词：肝豆状核变性 儿童 肝疾病 血清铜蓝蛋白 体征和症状 病理学 神经病学表现 基因 突变 

分 类 号：R742.4[医药卫生—神经病学与精神病学]