Wilson’s disease

Czech version

Authors: Z. Mareček ¹; R. Brůha ²
Authors‘ workplace: KlinMed s. r. o., Praha, vedoucí prof. MU Dr. Zdeněk Mareček, DrSc. ¹; IV. interní klinika 1. lékařské fakulty UK a VFN Praha, přednosta prof. MU Dr. Aleš Žák, DrSc. ²
Published in: Vnitř Lék 2013; 59(7): 578-583
Category:

Overview

Wilson’s 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 Wilson’s disease have been described. The most common mutation in Central Europe concerns H1069Q. The symptoms of Wilson’s 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 diagnosis is based on clinical and laboratory assessments (neurological signs, liver lesions, low ceruloplasmin, increased free serum copper, high Cu volumes in urine, Kayser‑Fleischer ring). The diagnosis is confirmed by a high Cu level in liver tissue or genetic proof. Untreated Wilson’s 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.

Key words:
Wilson’s disease – treatment – D‑penicillamine – zinc

Sources

1. Wilson SA. Progressive lenticular degeneration: a familial nervous disease associated with cirrhosis of the liver. Lancet 1912; 1: 1115– 1119.

2. Culota VC, Gitlin JD. Disorders of copper transport. In: Scriver CS (ed). The molecular and metabolic basis of inherited disease. New York: McGraw‑Hill 2001: 3105– 3126.

3. Schaefer M, Hopkins RG, Failla ML et al. Hepatocyte‑specific localisation and copper‑dependent trafficking of the Wilson’s disease protein in the liver. Am J Physiol 1999; 276: G639– G646.

4. Tanzi RE, Petrukhin K, Chernov I et al. The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene. Nat Genet 1993; 5: 344– 350.

5. Bull PC, Thomas GR, Rommens JM et al. The Wilson disease gene is a putative copper transporting P‑type ATPase similar to the Menkes gene. Nat Genet 1993; 5: 327– 337.

6. Mareček Z. Wilsonova choroba. Praha: Galén 1996.

7. Bruha R, Vitek L, Marecek Z et al. Decreased serum antioxidant capacity in patients with Wilson disease is associated with neurological symptoms. J Inherit Metab Dis 2012; 35: 541– 548.

8. Janda J, Kotalová R, Nevoral J et al. Akutní hemolytická krize se selháním jater jako první manifestace morbus Wilson u dětí. Čs Pediat 1996; 51: 509– 514.

9. Walter U, Krolikowski K, Tarnacka B et al. Sonographic detection of basal ganglia lesions in asymptomatic and symptomatic Wilson disease. Neurology 2005; 64: 1726– 1732.

10. Nevsimalova S, Buskova J, Bruha R et al. Sleep disorders in Wilson’s disease. Eur J Neurol 2011; 18: 184– 190.

11. Ferenci P, Caca K, Loudianos G et al. Diagnosis and phenotypic classification of Wilson disease. Liver 2003; 23: 139– 142.

12. Roberts EA, Schilsky ML. A practice guideline on Wilson disease. Hepatology 2003; 37: 1475– 1492.

13. Vrabelova S, Letocha O, Borsky M et al. Mutation analysis of the ATP7B gene and genotype/ phenotype correlation in 227 patients with Wilson disease. Mol Genet Metab 2005; 86: 277– 285.

14. Gojova L, Jansova E, Külm M et al. Genotyping microarray as a novel approach for the detection of ATP7B gene mutations in patients with Wilson disease. Clin Genet 2008; 73: 441– 452.

15. Bruha R, Marecek Z, Pospisilova L et al. Long‑term follow‑up of Wilson disease: natural history, treatment, mutations analysis and phenotypic correlation. Liver Int 2011; 31: 83– 91.

16. Wiggelinkhuizen M, Tilanus ME, Bollen CW et al. Systematic review: clinical efficacy of chelator agents and zinc in the initial treatment of Wilson disease. Aliment Pharmacol Ther 2009; 29: 947– 958.

17. Petrasek J, Jirsa M, Sperl J et al. Revisited Kings’s College score for liver transplantation in adult patients with Wilson’s disease. Liver Transpl 2007; 13: 55– 61.

18. Geissler I, Heinemann K, Rohm S et al. Liver transplantation for hepatic and neurological Wilson’s disease. Transplant Proc 2003; 35: 1445– 1446.

19. Hoogenraad TU. Zinc treatment of Wilson’s disease. J Lab Clin Med 1998; 132: 240– 241.

20. Brewer GJ, Dick RD, Johnson VD et al. Treatment of Wilson’s disease with zinc: XV long‑term follow‑up studies. J Lab Clin Med 1998; 132: 264– 278.

21. Huster D, Leonhardt K, Mossner J. Wilson disease – update on pathophysiology and management. Čes Slov Gastroent Hepatol 2008; 62: 220– 228.

22. Merle U, Schaefer M, Ferenci P et al. Clinical presentation, diagnosis and long‑term out-come of Wilson’s disease: a cohort study. Gut 2007; 56: 115– 120.

23. Lutsenko S, Petris MJ. Function and regulation of the mammalian copper transporting ATPases: insights from biochemical and cell biological approaches. J. Membran Biol 2002; 191: 1–12.