Smolarek C, Stremmel W
Universität Heidelberg, Abteilung Innere Medizin IV.
Z Gastroenterol. 1999 Apr;37(4):293-300.
Wilson disease is a copper storage disease with autosomal-recessive trait that is predominantly a disorder of the adolescent and young adult. Clinical manifestations are dominated by hepatic and/or neurological symptoms. Diagnostic procedures include determination of total serum copper, free serum copper and serum ceruloplamin concentrations as well as urinary copper excretion. Confirmation of diagnosis may be achieved by liver biopsy and histological determination of copper content. The aim of treatment is reduction of tissue copper concentration and detoxification of copper. Drugs applied are the chelating agents. D-penicillamine and trientine, or zinc. The chelating agents induce renal and biliary copper excretion and increased synthesis of metallothionein, which attaches and detoxifies intracellular copper, leading to impaired absorption and binding of excess intracellular copper. Treatment with zinc results in induction of hepatic and intestinal metallothionein synthesis. Regular examinations of the parameters of copper metabolism are necessary in order to control the therapeutic effect. Free copper serum concentrations and urinary copper excretion should reach values below 10 micrograms/dl and 80 micrograms/day, respectively. A significant improvement of clinical symptoms and normalization of parameters of copper metabolism can be expected earliest six months after onset of therapy. Anti-copper treatment may be accompanied by copper-reduced diet. Lifelong therapy is required and provides life-expectancy near to normal. Interruption of treatment leads to reaccumulation of copper, often resulting in fulminant hepatic failure. This can also be observed as initial presentation in 5% of cases (predominant age 12 to 25 years). End stage liver disease and fulminant hepatic failure are indications for liver transplantation by which the genetic defect is phenotypically cured. Here decoppering treatment is no longer required. Whether severe neurological disorders may also be improved is not clear until today.
威尔逊病是一种具有常染色体隐性遗传特征的铜贮积病，主要发生于青少年和青年成人。临床表现以肝脏和/或神经症状为主。诊断程序包括测定血清总铜、游离血清铜和血清铜蓝蛋白浓度以及尿铜排泄量。肝活检及铜含量的组织学测定可确诊。治疗目的是降低组织铜浓度并使铜解毒。应用的药物有螯合剂，如青霉胺和曲恩汀，或锌。螯合剂可促使肾脏和胆汁排铜，并增加金属硫蛋白的合成，金属硫蛋白可结合细胞内铜并使其解毒，从而减少细胞内过量铜的吸收和结合。锌治疗可诱导肝脏和肠道金属硫蛋白的合成。为控制治疗效果，有必要定期检查铜代谢参数。游离血清铜浓度和尿铜排泄量应分别降至10微克/分升和80微克/天以下。最早在治疗开始6个月后，临床症状有望显著改善，铜代谢参数恢复正常。抗铜治疗可辅以低铜饮食。需要终身治疗，可使预期寿命接近正常。中断治疗会导致铜重新蓄积，常引发暴发性肝衰竭。这在5%的病例中也可作为首发表现（主要发病年龄为12至25岁）。终末期肝病和暴发性肝衰竭是肝移植的指征，通过肝移植可从表型上治愈遗传缺陷。此时不再需要驱铜治疗。直至今日，严重神经障碍是否也能改善尚不清楚。
