Department of Public Health, School of Medicine, Mashhad University of Medical Sciences, Mashhad 93518-88415, Iran.
2nd Department of Neurology, Institute of Psychiatry and Neurology, 02-957 Warsaw, Poland.
Int J Mol Sci. 2022 Aug 18;23(16):9316. doi: 10.3390/ijms23169316.
Wilson's disease (WD) is a hereditary disorder of copper metabolism, producing abnormally high levels of non-ceruloplasmin-bound copper, the determinant of the pathogenic process causing brain and hepatic damage and dysfunction. Although the disease is invariably fatal without medication, it is treatable and many of its adverse effects are reversible. Diagnosis is difficult due to the large range and severity of symptoms. A high index of suspicion is required as patients may have only a few of the many possible biomarkers. The genetic prevalence of variants indicates higher rates in the population than are currently diagnosed. Treatments have evolved from chelators that reduce stored copper to zinc, which reduces the toxic levels of circulating non-ceruloplasmin-bound copper. Zinc induces intestinal metallothionein, which blocks copper absorption and increases excretion in the stools, resulting in an improvement in symptoms. Two meta-analyses and several large retrospective studies indicate that zinc is equally effective as chelators for the treatment of WD, with the advantages of a very low level of toxicity and only the minor side effect of gastric disturbance. Zinc is recommended as a first-line treatment for neurological presentations and is gaining acceptance for hepatic presentations. It is universally recommended for lifelong maintenance therapy and for presymptomatic WD.
威尔逊病（WD）是一种遗传性铜代谢紊乱疾病，导致非铜蓝蛋白结合铜水平异常升高，这是导致脑和肝损伤和功能障碍的致病过程的决定因素。尽管未经药物治疗，该疾病总是致命的，但它是可治疗的，其许多不良反应是可逆转的。由于症状的范围和严重程度很大，因此诊断困难。由于患者可能只有许多可能的生物标志物中的少数几种，因此需要高度怀疑。基因变异的遗传流行率表明，人群中的发病率高于目前的诊断率。治疗方法已经从减少储存铜的螯合剂发展到锌，锌可以降低循环中非铜蓝蛋白结合铜的毒性水平。锌诱导肠金属硫蛋白，阻止铜吸收并增加粪便排泄，从而改善症状。两项荟萃分析和几项大型回顾性研究表明，锌与螯合剂治疗 WD 的效果相当，其优点是毒性水平极低，仅有轻微的胃部不适副作用。锌被推荐作为神经表现的一线治疗药物，并逐渐被接受用于肝脏表现。它被普遍推荐用于终身维持治疗和无症状 WD。
