1Wilson disease
Section snippets
Copper balance and pathogenesis of Wilson disease
Daily uptake of copper in the proximal parts of the small intestine ranges between one and two milligrams, this amount is adequate for the needs of the human body. *[9], [10] In the blood copper is bound to amino acids (e.g. histidine) or proteins (e.g. albumin) and transported to the liver and peripheral tissues. [11] Due to its redox potential copper is essential for many physiological processes and serves as co-factor for important metabolic enzymes such as cytochrom c oxidase (mitochondrial
Inheritance and epidemiology of the ATP7B gene defect
The worldwide prevalence is estimated one in 30,000 and even higher in certain populations with consanguinity. The gene frequency in the healthy population is about one in 90. [21] ATP7B is located on the long arm of chromosome 13 (13q14–q21). To date more than 300 different mutations have been identified in the large ATP7B gene (cDNA: 4.4 kbp) (http://www.wilsondisease.med.ualberta.ca/database.asp). [22] Only few of these mutations were already functionally characterised. [23], [24], [25], [26]
Clinical presentation
Symptoms, clinical course and outcome of Wilson are highly variable. In principle, the main features – the hepatic and the neurologic form – can be distinguished, but many patients present with a mixture of both. Usually after an asymptomatic early life period predominant hepatic forms (manifestation between eight and 18 years) appear several years earlier than the neurologic forms (manifestation during early adulthood). [28], *[29], [30], [31] Late onset of symptomatic Wilson disease may occur
Diagnosis
Diagnostic delays appear frequently particularly in predominant neurologic manifestation of Wilson disease and result in poor clinical outcome. [36] Recognising Wilson disease is challenging. The clinician’s alertness and screening for Wilson disease in patients with suspect neurologic symptoms or unknown liver disease may prevent an unfavourable course of this treatable disease. A summary of diagnostic steps in different clinical situations is shown in Fig. 3.
Therapeutic strategies
All Wilson disease patients – even in the presymptomatic stage – need lifelong drug therapy. In general pharmacological treatment alternatives include copper chelators and zinc salts. Essential for long-term success of pharmacological treatment for Wilson disease is the patients’ adherence. Currently only liver transplantation is able to cure the disease (hepatic form). However, transplantation is only mandatory in some special situations (see below).
Conflict of interest
None.
Acknowledgement
This work was supported by the German Research Foundation (DFG HU 932/3-2).
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