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.

• MeSH
• chelátory terapeutické užití   MeSH
• hepatolentikulární degenerace diagnóza   genetika   patofyziologie   MeSH
• kvalita života psychologie   MeSH
• lidé MeSH
• měď škodlivé účinky   metabolismus   MeSH
• molybden terapeutické užití   MeSH
• potravní doplňky MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• chelátory MeSH
• měď MeSH
• molybden MeSH
• tetrathiomolybdate MeSH Prohlížeč

Wilson's disease (WD) is an inherited metabolic disorder related to disturbances of copper metabolism, and predominantly presents with liver and neuropsychiatric symptoms. In most cases it can be successfully treated with anti-copper agents, and both liver function and neuropsychiatric symptoms typically improve. Treatment guidelines for WD include recommendations for anti-copper treatment as well as for the treatment of liver failure symptoms. Recently, recommendations for treatment of the neurological symptoms of WD have also been proposed. Although most WD patients present with psychiatric symptoms at some stage of the disease, currently there are no guidelines for the treatment of the psychiatric manifestations. Treatment of the psychiatric symptoms of WD is often guided by general psychiatric experience, which typically glosses over the specificity of WD, and can result in severe neurological and/or hepatic complications. Here we review and discuss the possible treatments available for the mood disturbances, psychosis, behavioral and cognitive disorders that can occur in WD, as well as their efficacy.

• Klíčová slova
• Wilson’s disease, behavioral disturbances, cognitive deficits, mood disturbances, psychiatric symptoms, psychosis, treatment,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND & AIMS: Wilson disease (WD) is an inherited disorder of copper disposition caused by an ATP7B transporter gene mutation, leading to copper accumulation in predisposed tissues. In addition to a genetic predisposition, other factors are likely to contribute to its clinical manifestation. The aim of the study was to assess whether oxidative stress affects the phenotypic manifestation of WD. METHODS: In 56 patients with WD (29 men; 26 with the hepatic form, 22 with the neurologic form, and eight asymptomatic; mean age 38.5 ± 12 years), total serum antioxidant capacity (TAC) and inflammatory parameters (hs-CRP, IL-1β, IL-2, IL-6, IL-10, and TNF-α) were analyzed and related to the clinical manifestation, and mutations of the ATP7B gene. The control group for the TAC and inflammatory parameters consisted of 50 age- and gender-matched healthy individuals. RESULTS: WD patients had a significantly lower TAC (p < 0.00001), lower IL-10 levels (p = 0.039), as well as both higher IL-1β (p = 0.019) and IL-6 (p = 0.005) levels compared to the control subjects. TNF-α, hs-CRP, and IL-2 did not differ from the controls. Patients with the neurological form of WD had a significantly lower TAC than those with the hepatic form (p < 0.001). In addition, the lower TAC was associated with the severity of the neurological symptoms (p = 0.02). No relationship between the inflammatory parameters and clinical symptoms was found. CONCLUSIONS: Data from our study suggest that the increased oxidative stress contributes significantly to the clinical manifestation of WD; as a lower TAC is associated with the neurological symptoms in WD patients.

• MeSH
• adenosintrifosfatasy genetika   MeSH
• antioxidancia metabolismus   MeSH
• ATPasy transportující měď MeSH
• dospělí MeSH
• genetická predispozice k nemoci MeSH
• hepatolentikulární degenerace krev   MeSH
• interleukin-10 metabolismus   MeSH
• interleukin-1beta metabolismus   MeSH
• interleukin-6 metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• měď metabolismus   MeSH
• mutace * MeSH
• nemoci nervového systému krev   MeSH
• oxidační stres MeSH
• proteiny přenášející kationty genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adenosintrifosfatasy MeSH
• antioxidancia MeSH
• ATP7B protein, human MeSH Prohlížeč
• ATPasy transportující měď MeSH
• interleukin-10 MeSH
• interleukin-1beta MeSH
• interleukin-6 MeSH
• měď MeSH
• proteiny přenášející kationty MeSH