Roy Debasish, Mukherjee Angshuman, Chakravarty Ambar
Department of Neurology, Vivekananda Institute of Medical Science, Kolkata, West Bengal, India.
Curr Neurol Neurosci Rep. 2025 Jun 12;25(1):40. doi: 10.1007/s11910-025-01424-8.
Wilson disease (WD), an uncommon autosomal recessive (AR) hereditary disorder characterized by abnormal accumulation of copper primarily in the liver and secondarily in other organs like the brain, is caused by a deficiency in the ATP7B transporter gene. The key to successful therapy is early diagnosis.
Mutant genes need to be inherited from both parents for phenotypic expression. The ATP7B gene located on chromosome 13q14.3 comprises 20 introns and 21 exons, encodes a protein of 165 amino acids, and this helps in incorporation of copper into ceruloplasmin, the copper binding protein. So far, more than 800 mutations have been reported, of which 380 have confirmed involvement in the pathogenesis of WD. The most common mutations are H1069Q and R778L in European and Asian populations respectively. Approximately 90%-98% of WD subjects are heterozygous, showing different mutations in each of the alleles encoding the ATP7B. Conversely, the phenotype and the penetrance of WD can be extremely variable. Even patients carrying two disease-causing mutations do not necessarily have a demonstrable alteration of copper metabolism. Considering the possibility of late-onset disease, asymptomatic cases, and phenotypic variability, it is crucial to evaluate previous and future generations of the index case. WD ranges from being asymptomatic in some patients to result in acute liver failure and/or a variety of neuropsychiatric disorders among others. Although WD may be present at any age, is more common between the ages of 5 and 35 years. However, it should be investigated in patients with liver failure of unknown cause and those with liver disease associated with neuropsychiatric symptomatology. Diagnosis requires a combination of clinical signs and symptoms, as well as relevant diagnostic tests such as measurement of serum ceruloplasmin, urinary excretion of copper, liver biopsy or genetic testing. Treatment is lifelong and includes chelating agents (penicillamine and trientine) and inhibitors of copper absorption (zinc salts). Liver transplant is an option for patients with end-stage liver disease. The key to successful therapy is early diagnosis.
威尔逊病（WD）是一种罕见的常染色体隐性（AR）遗传性疾病，其特征是铜主要在肝脏异常蓄积，其次在脑等其他器官蓄积，由ATP7B转运蛋白基因缺陷引起。成功治疗的关键是早期诊断。
突变基因需从双亲遗传才能表现出表型。位于13q14.3染色体上的ATP7B基因包含20个内含子和21个外显子，编码一种含165个氨基酸的蛋白质，有助于将铜掺入铜蓝蛋白（铜结合蛋白）。到目前为止，已报道了800多种突变，其中380种已证实与WD的发病机制有关。欧洲和亚洲人群中最常见的突变分别是H1069Q和R778L。约90%-98%的WD患者为杂合子，在编码ATP7B的每个等位基因中表现出不同的突变。相反，WD的表型和外显率差异极大。即使携带两个致病突变的患者也不一定有明显的铜代谢改变。考虑到迟发性疾病、无症状病例和表型变异性的可能性，评估索引病例的前代和后代至关重要。WD在一些患者中可能无症状，在另一些患者中则会导致急性肝衰竭和/或各种神经精神障碍等。虽然WD可在任何年龄出现，但多见于5至35岁之间。然而，对于病因不明的肝衰竭患者以及伴有神经精神症状的肝病患者应进行检查。诊断需要结合临床体征和症状以及相关诊断测试，如血清铜蓝蛋白测定、尿铜排泄、肝活检或基因检测。治疗是终身的，包括螯合剂（青霉胺和曲恩汀）和铜吸收抑制剂（锌盐）。肝移植是终末期肝病患者的一种选择。成功治疗的关键是早期诊断。
