Schilsky M L
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Semin Liver Dis. 1996 Feb;16(1):83-95. doi: 10.1055/s-2007-1007221.
The discovery that the gene for Wilson disease encodes a copper-transporting ATPase has greatly improved our understanding of the pathophysiology of this disorder and of copper metabolism in humans. The abundance of disease-specific mutations and their location at multiple sites across the genome have limited molecular genetic diagnosis to kindred of known patients, and confirm the necessity for de novo screening by well-proven clinical and biochemical means. It is uncertain whether the variety of specific mutations will account for the wide range of presenting clinical signs and symptoms of Wilson disease, and environmental and extragenic factors are likely to be important contributing factors. Chelation therapy with penicillamine and trientine remain effective treatment for most symptomatic hepatic and neurologic Wilson disease. Zinc salts may be used for some asymptomatic patients, and OLT for fulminant hepatitis and patients for whom pharmacotherapy is ineffective. The chelating agent tetrathiomolybdate is under investigation for the treatment of neurologic Wilson disease. Gene therapy is the new horizon for treatment of Wilson disease. However, the ability to treat this disorder effectively by this means awaits further characterization of the gene product and more efficient methods for gene delivery to all hepatocytes in the liver.
威尔逊病基因编码一种铜转运ATP酶这一发现，极大地增进了我们对该疾病病理生理学以及人类铜代谢的理解。疾病特异性突变数量众多且分布于基因组多个位点，这使得分子遗传学诊断仅限于已知患者的亲属，也证实了通过成熟的临床和生化方法进行从头筛查的必要性。尚不确定各种特定突变是否能解释威尔逊病广泛的临床症状和体征，环境和基因外因素可能是重要的促成因素。青霉胺和曲恩汀的螯合疗法对大多数有症状的肝型和神经型威尔逊病仍然是有效的治疗方法。锌盐可用于一些无症状患者，肝移植可用于暴发性肝炎患者以及药物治疗无效的患者。螯合剂四硫钼酸盐正在用于神经型威尔逊病治疗的研究中。基因治疗是威尔逊病治疗的新方向。然而，要通过这种方式有效治疗该疾病，还需进一步明确基因产物的特性，并找到更有效的将基因传递至肝脏所有肝细胞的方法。
