INTRODUCTION: Wilson's disease (WD) is a potentially treatable, inherited disorder resulting from impaired copper metabolism. Pathological copper accumulation causes a range of symptoms, most commonly hepatic and a wide spectrum of neurological symptoms including tremor, dystonia, chorea, parkinsonism, dysphagia, dysarthria, gait and posture disturbances. To reduce copper overload, anti-copper drugs are used that improve liver function and neurological symptoms in up to 85% of patients. However, in some WD patients, treatment introduction leads to neurological deterioration, and in others, neurological symptoms persist with no improvement or improvement only after several years of treatment, severely affecting the patient's quality of life. AREAS COVERED: This review appraises the evidence on various pharmacological and non-pharmacological therapies, neurosurgical procedures and liver transplantation for the management of neurological WD symptoms. The authors also discuss the neurological symptoms of WD, causes of deterioration and present symptomatic treatment options. EXPERT OPINION: Based on case and series reports, current recommendations and expert opinion, WD treatment is focused mainly on drugs leading to negative copper body metabolism (chelators or zinc salts) and copper-restricted diet. Treatment of WD neurological symptoms should follow general recommendations of symptomatic treatment. Patients should be always considered individually, especially in the case of severe, disabling neurological symptoms.
- Klíčová slova
- Wilson’s disease, dysphagia, dysarthria, dystonia, chorea, parkinsonism, neurological symptoms, symptomatic treatment,
- MeSH
- chelátory terapeutické užití MeSH
- dystonické poruchy * MeSH
- hepatolentikulární degenerace * komplikace terapie diagnóza MeSH
- kvalita života MeSH
- lidé MeSH
- měď metabolismus terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- chelátory MeSH
- měď MeSH
Wilson disease (WD) is a potentially treatable neurodegenerative disorder. In the majority of cases, treatment with drugs that induce a negative copper balance (usually chelators or zinc salts) leads to improvements in liver function and neurologic signs. However, some patients show severe neurologic symptoms at diagnosis, such as tremor, dystonia, parkinsonism, and chorea. In this patient group, some neurologic deficits may persist despite adequate treatment, and further neurologic deterioration may be observed after treatment initiation. Such patients may require additional treatment to alleviate neurologic symptoms. Apart from general recommendations for WD anticopper treatment, there are currently no guidelines for managing neurologic symptoms in WD. The aim of this chapter is to summarize possible treatments of neurologic symptoms in WD based on the presently available medical literature.
- Klíčová slova
- Wilson disease, botulinum toxin, deep-brain stimulation, dopamine, dystonia, parkinsonism, tremor,
- MeSH
- chelátory terapeutické užití MeSH
- dystonické poruchy terapie MeSH
- dystonie terapie MeSH
- hepatolentikulární degenerace komplikace terapie MeSH
- lidé MeSH
- nemoci nervového systému terapie MeSH
- tremor terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- chelátory MeSH
Trace elements, such as iron, copper, manganese, and calcium, which are essential constituents necessary for cellular homeostasis, become toxic when present in excess quantities. In this article, we describe disorders arising from endogenous dysregulation of metal homeostasis leading to their tissue accumulation. Although subgroups of these diseases lead to regional brain metal accumulation, mostly in globus pallidus, which is susceptible to accumulate divalent metal ions, other subgroups cause systemic metal accumulation affecting the whole brain, liver, and other parenchymal organs. The latter group comprises Wilson disease, manganese transporter deficiency, and aceruloplasminemia and responds favorably to chelation treatment.
- Klíčová slova
- Chelating therapy, Manganism, NBIA, Neurodegeneration with brain iron accumulation, Primary familial brain calcification, Wilson disease,
- MeSH
- chelátová terapie MeSH
- duševní poruchy etiologie MeSH
- hepatolentikulární degenerace epidemiologie etiologie patofyziologie terapie MeSH
- kovy metabolismus toxicita MeSH
- lidé MeSH
- mozek metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- audiovizuální média MeSH
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- kovy MeSH
Wilsons disease is an autosomal recessive genetic disorder in which copper accumulates in tissues, especially in the liver and the brain. The genetic defect affects the P type ATPase gene (ATP7B). More than 500 mutations causing Wilsons disease have been described. The most common mutation in Central Europe concerns H1069Q. The symptoms of Wilsons disease include hepatic or neurological conditions. The hepatic condition is manifested as steatosis, acute or chronic hepatitis or cirrhosis. The neurological conditions are most often manifested after the age of 20 as motor disorders (tremor, speech and writing disorders), which may result in severe extrapyramidal syndrome with rigidity, dysarthria and muscle contractions. The dia-gnosis is based on clinical and laboratory assessments (neurological signs, liver lesions, low ceruloplasmin, increased free serum copper, high Cu volumes in urine, KayserFleischer ring). The dia-gnosis is confirmed by a high Cu level in liver tissue or genetic proof. Untreated Wilsons disease causes death of the patient. If treated properly the survival rate approximates to the survival rate of the common population. The treatment concerns either removal of copper from the body using chelating agents excreted into the urine (Penicillamine, Trientine) or limitation of copper absorption from the intestine and reducing the toxicity of copper (zinc, ammonium tetrathiomolybdate). In the Czech Republic, Penicillamine or zinc is used. A liver transplant is indicated in patients with fulminant hepatic failure or decompensated liver cirrhosis. In the family all siblings of the affected individual need to be screened in order to treat any asymptomatic subjects.
- MeSH
- adenosintrifosfatasy genetika MeSH
- ATPázy transportující měď MeSH
- chelátory terapeutické užití MeSH
- dospělí MeSH
- hepatolentikulární degenerace diagnóza genetika terapie MeSH
- jaterní cirhóza chirurgie MeSH
- lidé MeSH
- měď metabolismus MeSH
- molybden terapeutické užití MeSH
- mutace MeSH
- penicilamin terapeutické užití MeSH
- proteiny přenášející kationty genetika MeSH
- transplantace jater * MeSH
- trientin terapeutické užití MeSH
- zinek terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Geografické názvy
- Česká republika MeSH
- Názvy látek
- adenosintrifosfatasy MeSH
- ATP7B protein, human MeSH Prohlížeč
- ATPázy transportující měď MeSH
- chelátory MeSH
- měď MeSH
- molybden MeSH
- penicilamin MeSH
- proteiny přenášející kationty MeSH
- tetrathiomolybdate MeSH Prohlížeč
- trientin MeSH
- zinek MeSH
BACKGROUND AND AIMS: Wilson disease (WD) is an inherited disorder of copper metabolism. When treated, the outcome can be excellent, although the long-term survival has yet to be well documented. The aim of this study was to describe the long-term outcome of a cohort of patients with WD and to assess those factors affecting the phenotypic manifestation of WD. METHODS: The presence of mutations to the ATP7B gene, the clinical manifestations, treatments and the long-term outcomes were analysed retrospectively in 117 patients with WD (59 men and 58 women, aged at evaluation 38.5 ± 11, range 16-63 years). RESULTS: Fifty-five patients with a neurological presentation, 51 patients with a hepatic presentation and 11 asymptomatic patients were followed up for an average of 15.1 ± 10 years (median 12 years, range 1-41 years). The H1069Q ATP7B gene mutation was the most frequent genetic variant (54.3%); the frequency of this mutation did not differ between patients with either the hepatic or the neurological presentation (P = 0.099). d-penicillamine or zinc salts (81 and 17% respectively) were used for treatment, and three patients underwent liver transplantation. The majority of symptomatic patients became asymptomatic, or improved, during the follow-up (82% patients with hepatic presentation, 69% with neurological presentation). The long-term survival of patients with WD did not differ from that of the general Czech population (P = 0.95). CONCLUSIONS: Long-term follow-up shows a satisfactory response in the great majority of adequately treated patients with WD and survival coincides with that of the general population.
- MeSH
- adenosintrifosfatasy genetika metabolismus MeSH
- asymptomatické nemoci MeSH
- ATPázy transportující měď MeSH
- časové faktory MeSH
- chelátory metabolismus MeSH
- dospělí MeSH
- fenotyp MeSH
- frekvence genu MeSH
- genetická predispozice k nemoci MeSH
- hepatolentikulární degenerace enzymologie genetika mortalita terapie MeSH
- Kaplanův-Meierův odhad MeSH
- lidé středního věku MeSH
- lidé MeSH
- měď metabolismus MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mutace * MeSH
- mutační analýza DNA MeSH
- octan zinečnatý terapeutické užití MeSH
- penicilamin terapeutické užití MeSH
- progrese nemoci MeSH
- proteiny přenášející kationty genetika metabolismus MeSH
- retrospektivní studie MeSH
- rozdělení chí kvadrát MeSH
- síran zinečnatý terapeutické užití MeSH
- transplantace jater MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
- Názvy látek
- adenosintrifosfatasy MeSH
- ATP7B protein, human MeSH Prohlížeč
- ATPázy transportující měď MeSH
- chelátory MeSH
- měď MeSH
- octan zinečnatý MeSH
- penicilamin MeSH
- proteiny přenášející kationty MeSH
- síran zinečnatý MeSH
Fulminant Wilson's disease (WD) is almost invariably fatal, and liver transplantation is the only life-saving treatment. Decompensated chronic WD usually responds to chelation therapy. Our aim was to validate 3 published scoring systems for deciding between chelation treatment and liver transplantation in patients with chronic decompensated and fulminant WD. Model for end-stage liver disease (MELD) score, as well as WD prognostic index (WPI) and its recently revised version (RWPI) were evaluated as predictors of the safety for chelation therapy. A group of 14 adult patients with decompensated chronic WD who improved on penicillamine treatment were compared with 21 patients with fulminant WD. The diagnosis of WD was based on increased urinary copper excretion and confirmed by elevated liver copper content and/or mutation analysis of the WD gene. The MELD score, WPI, and RWPI were calculated for all patients with WD. The accuracy of the MELD score, WPI, and RWPI for prediction of response to chelation therapy in patients with decompensated chronic WD was 0.968, 0.980, and 0.993, respectively. None of the decompensated chronic WD patients had a MELD score >30, RWPI >11, or WPI >7. RWPI showed the highest accuracy and the lowest false negativity compared with WPI and MELD. In conclusion, our data indicate that RWPI, originally proposed for pediatric patients, is also useful for adults.
- MeSH
- dospělí MeSH
- genotyp MeSH
- hepatolentikulární degenerace diagnóza chirurgie terapie MeSH
- játra metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- měď metabolismus MeSH
- mladiství MeSH
- mutace * MeSH
- mutační analýza DNA MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- selhání jater chirurgie terapie MeSH
- senioři MeSH
- transplantace jater metody MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- měď MeSH
The authors describe the case of a 27-year-old female patient with Wilson's disease who during penicillinamine treatment became pregnant and was delivered of a healthy infant. The diagnosis of Wilson's disease was confirmed by the finding of a Kayser-Fleischer ring in the cornea and a concurrent serum ceruloplasmin concentration lower than 0.20 g/l. Unrecognized and untreated, the disease is associated with the development of organ complications which in the end prove fatal. On the other hand, early diagnosis and effective treatment throughout life can prevent liver and brain damage and thus enable the patient to live a normal life and women can have a healthy child.
- MeSH
- dospělí MeSH
- hepatolentikulární degenerace * terapie MeSH
- komplikace těhotenství * terapie MeSH
- lidé MeSH
- těhotenství MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- kazuistiky MeSH
