Wilson disease (WD) is a potentially treatable, inherited disorder of copper metabolism that is characterized by the pathological accumulation of copper. WD is caused by mutations in ATP7B, which encodes a transmembrane copper-transporting ATPase, leading to impaired copper homeostasis and copper overload in the liver, brain and other organs. The clinical course of WD can vary in the type and severity of symptoms, but progressive liver disease is a common feature. Patients can also present with neurological disorders and psychiatric symptoms. WD is diagnosed using diagnostic algorithms that incorporate clinical symptoms and signs, measures of copper metabolism and DNA analysis of ATP7B. Available treatments include chelation therapy and zinc salts, which reverse copper overload by different mechanisms. Additionally, liver transplantation is indicated in selected cases. New agents, such as tetrathiomolybdate salts, are currently being investigated in clinical trials, and genetic therapies are being tested in animal models. With early diagnosis and treatment, the prognosis is good; however, an important issue is diagnosing patients before the onset of serious symptoms. Advances in screening for WD may therefore bring earlier diagnosis and improvements for patients with WD.
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The authors acknowledge the following grant support: A.C. and T.L. (NCN 2013/11/B and NZ2/00130); S.L. (US NIH grant DK071865), P.D. (Czech Ministry of Health, nr.15-25602A) and V.M. (US NIH grant DK104770-02). Assistance with administration, reference management and English language provided by E. Marshman, which was funded by the Institute of Psychiatry and Neurology (Poland) as a statutory activity.
Nature Reviews Disease Primers thanks P. Wittung-Stafshede, M. Svetel, R.H.J.H. Houwen, R. Iorio and the other anonymous reviewer(s) for their contribution to the peer review of this work.
A.C. has served on advisory boards for Wilson Therapeutics, Vivet Therapeutics and GMP-Orphan SAS and has received speaker fees from EVER Pharma, Boehringer Ingelheim and Nutricia. P.F. has served on advisory boards for Wilson Therapeutics, Vivet Therapeutics and Univar and has received speaker fees from Univar. V.M. has served as a consultant for Kadmon Holdings. K.H.W. is on the speakers bureaus of AbbVie, Alexion Pharmaceuticals, Bayer, Bristol-Myers Squibb, Chiesi Farmaceutici SpA, GMP-Orphan SAS, Norgine, Novartis, Univar, Wilson Therapeutics and Vivet Therapeutics and has received grants (to the institution) from Alexion Pharmaceuticals, Bayer, Bristol-Myers Squibb, Eisai, GMP-Orphan SAS, Novartis, Univar and Wilson Therapeutics. M.L.S. has served on advisory boards for Wilson Therapeutics, Vivet Therapeutics, GMP-Orphan SAS and Kadmon Holdings, is a speaker for Gilead Sciences and is on the Medical Advisory Committee of the Wilson Disease Association. All other authors declare no competing interests.
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Członkowska, A., Litwin, T., Dusek, P. et al. Wilson disease. Nat Rev Dis Primers 4, 21 (2018). https://doi.org/10.1038/s41572-018-0018-3
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