Wilson's Disease.

Wilson's disease (WD) is an autosomal recessive inherited disorder leading to impaired intrahepatic trafficking and biliary excretion of copper, resulting in the accumulation of copper in various organs including the liver, cornea, and brain. The WD gene (OMIM 277900) codes for a copper transporting P-type ATPase (ATP7B). Although the finding of the gene resulted in a major breakthrough for understanding the pathophysiology of WD, the role of genetic testing in the clinical management of WD patients is not yet established. There is no gold standard for diagnosis of WD. Diagnosis requires a combination of clinical and biochemical tests. None of these parameters alone allows a certain diagnosis of WD. To facilitate diagnosis, a scoring system was developed at the 8th International Meeting on Wilson Disease in Leipzig, Germany in 2001. For clinical purposes, the use of mutation analysis is limited by the occurrence of many mutations (more than 200) causing WD. In contrast to direct DNA sequencing, direct mutation detection by using allele-specific probes is rapid and clinically very helpful, if a mutation occurs with a reasonable frequency in the population (ie, H1069Q in European WD patients or R778L in WD patients from the Far East). To date, mutation analysis is the only reliable tool for screening the family of an index case with known causative mutation. Alternatively, haplotype analysis can be used to address diagnostic dilemmas in differentiating heterozygote gene carriers and affected asymptomatic siblings.