Diagnosis and phenotypic classification of Wilson disease
Diagnosis and phenotypic classification of Wilson disease
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DOI：
10.1034/j.1600-0676.2003.00824.x
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发表时间：
2003-06-01
影响因子：
6.7
通讯作者：
Berr, F
中科院分区：
文献类型：
--
作者：
Ferenci, P;Caca, K;Berr, F
威尔逊病是一种遗传性常染色体隐性疾病的肝脏铜代谢导致铜积聚在肝细胞和肝外器官，如大脑和角膜。最初威尔逊病被描述为一种与肝硬化相关的神经退行性疾病。后来，在儿童和青少年中观察到肝豆状核变性，表现为急性或慢性肝病，没有任何神经系统症状。虽然神经性威尔逊病的诊断是直截了当的，但在非神经性病例中可能相当困难。到目前为止，没有单一的诊断测试可以100%排除或确认威尔逊病。1993年，威尔森病的基因被克隆并定位在染色体13q14.3 （MIM277900）上（1,2）。威尔逊病基因ATP7B编码p型atp酶。迄今为止，已有超过200种引起该基因突变的疾病被描述(3)。这些突变大多发生在单家族中，只有少数更常见（如高加索人的H1069Q， 3400delC和2299insC（4-6）或日本(7)，中国和韩国患者的R778L）。表型-基因型关系的研究受到缺乏标准诊断标准和表型分类的阻碍。为了克服这一问题，一个工作组在2001年4月16日至18日在德国莱比锡举行的第8届Wilson病和Menkes病国际会议上深入讨论了这些问题(2)。会议结束后，向所有积极的与会者邮寄了协商一致报告的初稿，并将他们的评论纳入最后案文。
Wilson disease is an inherited autosomal recessive disorder of hepatic copper metabolism leading to copper accumulation in hepatocytes and in extrahepatic organs such as the brain and the cornea. Originally Wilson disease was described as a neurodegerative disorder associated with cirrhosis of the liver. Later, Wilson disease was observed in children and adolescents presenting with acute or chronic liver disease without any neurologic symptoms. While diagnosis of neurologic Wilson disease is straightforward, it may be quite difficult in non-neurologic cases. Up to now, no single diagnostic test can exclude or confirm Wilson disease with 100% certainty. In 1993, the gene responsible for Wilson disease was cloned and localized on chromosome 13q14.3 (MIM277900) (1, 2). The Wilson disease gene ATP7B encodes a P-type ATPase. More than 200 disease causing mutations of this gene have been described so far (3). Most of these mutations occur in single families, only a few are more frequent (like H1069Q, 3400delC and 2299insC in Caucasian (4-6) or R778L in Japanese (7), Chinese and Korean patients). Studies of phenotype-genotype relations are hampered by the lack of standard diagnostic criteria and phenotypic classifications. To overcome this problem, a working party discussed these problems in depth at the 8th International Meeting on Wilson disease and Menkes disease in Leipzig/Germany (April 16-18, 2001)(2). After the meeting, a preliminary draft of a consensus report was mailed to all active participants and their comments were incorporated in the final text.