Whom and how to screen for Wilson disease

Abstract

Wilson disease is a genetic disorder of hepatic copper excretion leading to copper accumulation in various tissues. The disease expression is highly variable, ranging from totally asymptomatic subjects to patients with severe liver disease or movement disorders. Thus, it is difficult to define in which patient Wilson disease has to be considered as diagnosis. The suspicion should be high in patients presenting with extrapyramidal disorders or with liver diseases or of unknown origin. For diagnosis, in many patients a combination of tests reflecting disturbed copper metabolism may be needed. Not a single test is per se specific and, thus, a range of tests has to be applied (presence or absence of Kayser–Fleischer rings or neurologic symptoms, serum ceruloplasmin, liver copper content, urinary copper excretion, mutation analysis; rated –1 to 4 depending on the test) and clinical symptoms. A diagnostic sum score of ≥4 confirms the diagnosis.

Keywords::

• ceruloplasmin
• genetics
• hepatic copper content
• Kayser–Fleischer rings
• Wilson disease

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Wilson disease may present at any age with a whole spectrum of different (nonspecific) symptoms.

• Hepatic Wilson disease lacks many of the typical signs (like Kayser–Fleischer rings) and findings (like low ceruloplasmin) described in textbooks.

• Determination of ceruloplasmin by nephelometry is not a useful screening test for Wilson disease.

• The best diagnostic tests are the measurement of 24-h urinary copper excretion or of hepatic copper content.

• Genetic testing is the most reliable tool to diagnose (or to exclude) the disease in siblings of index cases.

• For many patients, a combination of tests reflecting disturbed copper metabolism may be needed. Not a single test is per se specific and, thus, a range of tests have to be applied. A diagnostic score calculated from the test results is recommended as the most useful diagnostic tool for Wilson disease.

Notes