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目的总结以肝病为首发表现的儿童肝豆状核变性(Wilson’s disease,WD)的临床、病理及基因突变特征,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-Fleischer(K-F)环及头颅MRI检查阳性率分别为20.0%和0%,>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。39.0%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24 h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 genetic features of Wilson’s disease (WD) in children with liver disease as the first manifestation, in order to improve the early diagnosis of these diseases. Methods A retrospective analysis of the clinical, pathological and genetic diagnosis of 317 WD patients aged 11 months to 16 years (median 9.0 years) with liver disease as the first manifestation in our hospital from January 2005 to January 2013 was retrospectively analyzed. data. Results Liver disease as the first manifestation of the disease in children without progression to advanced liver disease, no clinical symptoms before diagnosis WD, 25.9% of patients were misdiagnosed. 31.9% of children have anemia, 18.6% of children with renal injury, 90.9% of children with abnormal serum ceruloplasmin level. The positive rates of Kayser-Fleischer (K-F) ring and cranial MRI in ≤7 years old group were 20.0% and 0%, respectively, and those in> 7 years old group were 79.1% and 14.9% respectively. The major pathological changes of liver pathology showed varying degrees of chronic hepatitis. 44.5% of children had varying degrees of steatosis, 35.4% had severe hepatic fibrosis, 14.0% had active cirrhosis and 82.3% positive for copper staining. In 39.0% of the children, codon 778 of ATP7B gene appeared, 34.1% of them showed compound homozygous mutation and 4.9% showed Thr935Met codon mutation. Conclusion For any age children with unexplained elevated transaminases and cirrhosis, the exclusion of viral hepatitis should first consider the possibility of WD. Even if the level of ceruloplasmin is normal, negative K-F ring and cranial MRI examination can not completely rule out WD, further assessment of 24-hour urinary copper, penicillamine challenge test, liver pathology and ATP7B gene detection in children should be further evaluated.