Genetic testing for Wilson disease: availability and utility

Wilson disease, a genetic disorder of copper metabolism, presents typically in the second and third decades of life with hepatic or neuropsychiatric disease. Clinical presentations often vary depending on age and degree of onset; although clinical and biochemical testing can usually establish a diagnosis, the data are difficult to interpret in some patients. Correctly identifying patients from nonaffected carriers is important because treatment is lifelong. Genetic testing has greatly improved the ability to diagnose Wilson disease in affected patients and in their siblings even without clear-cut clinical and biochemical data. Direct sequencing of ATP7B for disease-specific mutations is now the standard for molecular diagnosis. However, haplotype analysis is useful when only a single mutation can be found. In specific populations with a higher frequency of a specific mutation, direct testing for these mutations can simplify and expedite molecular diagnosis. The molecular genetic test is now available commercially and in specific research laboratories; however, barriers to its use include cost, understanding when to perform it, and interpretation. This test eventually will be incorporated into the diagnostic armamentarium, allowing timely diagnosis and perhaps reversal or even prevention of further copper-induced injury.