Wilson Disease

Czech version

Authors: P. Dušek ¹; R. Brůha ²; Andrea Burgetová ³; D. Záhoráková ⁴; E. Růžička ¹
Authors‘ workplace: 1. LF UK a VFN v Praze Neurologická klinika a Centrum klinických neurověd ¹; 1. LF UK a VFN v Praze IV. interní klinika ²; 1. LF UK a VFN v Praze Radiodiagnostická klinika ³; 1. LF UK a VFN v Praze Klinika dětského a dorostového lékařství, Laboratoř pro studium mitochondriálních poruch ⁴
Published in: Cesk Slov Neurol N 2013; 76/109(5): 539-549
Category: Minimonography

Práce byla podpořena grantem Univerzity Karlovy PRVOUK-P26/LF1/4.

Overview

The Wilson disease is a rare hereditary metabolic disease with autosomal recessive inheritance. It is caused by a dysfunction of the ATP7B protein that hampers copper excretion into the bile ducts and its integration into the ceruloplasmin. Disease symptoms arise as a consequence of excess copper accumulation in various organs, especially in the liver and brain. Manifestations of the Wilson disease may be very diverse and it is necessary to consider this diagnosis in any patient aged 5– 50 years with extrapyramidal, cerebellar or psychiatric symptoms, especially in a setting of liver dysfunction. The most common neuropsychiatric symptoms include tremor, dysarthria, anxiety, depression, Parkinsonism, personality disorders, ataxia and dystonia. Final diagnosis requires the use of several auxiliary investigations: ophthalmic, genetic, brain magnetic resonance imaging and biochemical proof of disturbed copper metabolism. Early diagnosis and treatment is necessary to avoid irreversible brain and liver damage. The Wilson disease has an excellent prognosis subject to early therapy initiation and life- long regular monitoring of its effect.

Key words:
Wilson disease – neurologic manifestation – hepatolenticular degeneration – ATP7B mutation – chelation therapy

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.

Sources

1. Tanzi RE, Petrukhin K, Chernov I, Pellequer JL, Wasco W, Ross B et al. The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene. Nat Genet 1993; 5(4): 344– 350.

2. Bull PC, Thomas GR, Rommens JM, Forbes JR, Cox DW. The Wilson disease gene is a putative copper transporting P‑type ATPase similar to the Menkes gene. Nat Genet 1993; 5(4): 327– 337.

3. Coffey AJ, Durkie M, Hague S, McLay K, Emmerson J,Lo C et al. A genetic study of Wilson‘s disease in the United Kingdom. Brain 2013; 136(Pt 5): 1476– 1487.

4. Walshe JM. Wilson‘s disease. The presenting symptoms. Arch Dis Child 1962; 37: 253– 256.

5. Akil M, Schwartz JA, Dutchak D, Yuzbasiyan‑ Gurkan V, Brewer GJ. The psychiatric presentations of Wilson‘s disease. J Neuropsychiatry Clin Neurosci 1991; 3(4): 377– 382.

6. Bruha R, Marecek Z, Pospisilova L, Nevsimalova S, Vitek L, Martasek P et al. Long‑term follow‑up of Wilson disease: natural history, treatment, mutations analysis and phenotypic correlation. Liver Int 2011; 31(1): 83– 91.

7. Lalioti V, Sandoval I, Cassio D, Duclos‑ Vallee JC. Molecular pathology of Wilson‘s disease: a brief. J Hepatol 2010; 53(6): 1151– 1153.

8. Nagasaka H, Inoue I, Inui A, Komatsu H, Sogo T, Murayama K et al. Relationship between oxidative stress and antioxidant systems in the liver of patients with Wilson disease: hepatic manifestation in Wilson disease as a consequence of augmented oxidative stress. Pediatr Res 2006; 60(4): 472– 477.

9. Brewer GJ. A brand new mechanism for copper toxicity. J Hepatol 2007; 47(4): 621– 622.

10. Merle U, Stremmel W. Copper toxicity in Wilson disease explained in a new way. Hepatology 2011; 54(1): 358– 360.

11. Ferenci P, Czlonkowska A, Merle U, Ferenc S, Gromadzka G, Yurdaydin C et al. Late‑ onset Wilson‘s disease. Gastroenterology 2007; 132(4): 1294– 1298.

12. Lee BH, Kim JH, Lee SY, Jin HY, Kim KJ, Lee JJ et al. Distinct clinical courses according to presenting phenotypes and their correlations to ATP7B mutations in a large Wilson‘s disease cohort. Liver Int 2011; 31(6): 831– 839.

13. European Association for Study of Liver. EASL Clinical Practice Guidelines: Wilson‘s disease. J Hepatol 2012; 56(3): 671– 685.

14. Ala A, Walker AP, Ashkan K, Dooley JS, Schilsky ML. Wilson‘s disease. Lancet 2007; 369(9559): 397– 408.

15. Merle U, Schaefer M, Ferenci PStremmel W. Clinical presentation, diagnosis and long‑term outcome of Wilson‘s disease: a cohort study. Gut 2007; 56(1): 115– 120.

16. Burke JF, Dayalu P, Nan B, Askari F, Brewer GJ, Lorincz MT. Prognostic significance of neurologic examination findings in Wilson disease. Parkinsonism Relat Disord 2011; 17(7): 551– 556.

17. Barthel H, Hermann W, Kluge R, Hesse S, Collingridge DR, Wagner A et al. Concordant pre‑ and postsynaptic deficits of dopaminergic neurotransmission in neurologic Wilson disease. AJNR Am J Neuroradiol 2003; 24(2): 234– 238.

18. Lorincz MT. Neurologic Wilson‘s disease. Ann N Y Acad Sci 2010; 1184: 173– 187.

19. Akil M, Brewer GJ. Psychiatric and behavioral abnormalities in Wilson‘s disease. Adv Neurol 1995; 65: 171– 178.

20. Taly AB, Meenakshi‑ Sundaram S, Sinha S, Swamy HS, Arunodaya GR. Wilson disease: description of 282 patients evaluated over 3 decades. Medicine (Baltimore) 2007; 86(2): 112– 121.

21. Srinivas K, Sinha S, Taly AB, Prashanth LK, Arunodaya GR, Janardhana Reddy YC et al. Dominant psychiatric manifestations in Wilson‘s disease: a diagnostic and therapeutic challenge! J Neurol Sci 2008; 266(1– 2): 104– 108.

22. Svetel M, Potrebic A, Pekmezovic T, Tomic A, Kresojevic N, Jesic R et al. Neuropsychiatric aspects of treated Wilson‘s disease. Parkinsonism Relat Disord 2009; 15(10): 772– 775.

23. Eisenbach C, Sieg O, Stremmel W, Encke J, Merle U.Diagnostic criteria for acute liver failure due to Wilson disease. World J Gastroenterol 2007; 13(11): 1711– 1714.

24. Saito T. Presenting symptoms and natural history of Wilson disease. Eur J Pediatr 1987; 146(3): 261– 265.

25. Walshe JM. The eye in Wilson disease. QJM 2011; 104(5): 451– 453.

26. Roberts EA, Schilsky ML, American Association for Study of Liver D. Diagnosis and treatment of Wilson disease: an update. Hepatology 2008; 47(6): 2089– 2111.

27. Macintyre G, Gutfreund KS, Martin WR, Camicioli R,Cox DW. Value of an enzymatic assay for the determination of serum ceruloplasmin. J Lab Clin Med 2004; 144(6): 294– 301.

28. Martins da Costa C, Baldwin D, Portmann B, Lolin Y, Mowat AP, Mieli‑ Vergani G. Value of urinary copper excretion after penicillamine challenge in the diagnosis of Wilson‘s disease. Hepatology 1992; 15(4): 609– 615.

29. Ferenci P, Steindl‑ Munda P, Vogel W, Jessner W, Gschwantler M, Stauber R et al. Diagnostic value of quantitative hepatic copper determination in patients with Wilson‘s Disease. Clin Gastroenterol Hepatol 2005; 3(8): 811– 818.

30. Kenney SM, Cox DW. Sequence variation database for the Wilson disease copper transporter, ATP7B. Hum Mutat 2007; 28(12): 1171– 1177.

31. Vrabelova S, Letocha O, Borsky M, Kozak L. Mutation analysis of the ATP7B gene and genotype/ phenotype correlation in 227 patients with Wilson disease. Mol Genet Metab 2005; 86(1– 2): 277– 285.

32. Stapelbroek JM, Bollen CW, van Amstel JK, van Erpecum KJ, van Hattum J, van den Berg LH et al. The H1069Q mutation in ATP7B is associated with late and neurologic presentation in Wilson disease: results of a meta‑analysis. J Hepatol 2004; 41(5): 758– 763.

33. Czlonkowska A, Gromadzka G, Chabik G. Monozygotic female twins discordant for phenotype of Wilson‘s disease. Mov Disord 2009; 24(7): 1066– 1069.

34. Sinha S, Taly AB, Ravishankar S, Prashanth LK, Venugopal KS, Arunodaya GR et al. Wilson‘s disease: cranial MRI observations and clinical correlation. Neuroradiology 2006; 48(9): 613– 621.

35. Huang CC, Chu NS. Psychosis and epileptic seizures in Wilson‘s disease with predominantly white matter lesions in the frontal lobe. Parkinsonism Relat Disord 1995; 1(1): 53– 58.

36. Semnic R, Svetel M, Dragasevic N, Petrovic I, Kozic D,Marinkovic J et al. Magnetic resonance imaging morphometry of the midbrain in patients with Wilson disease. J Comput Assist Tomogr 2005; 29(6): 880– 883.

37. Prashanth LK, Sinha S, Taly ABVasudev MK. Do MRI features distinguish Wilson‘s disease from other early onset extrapyramidal disorders? An analysis of 100 cases. Mov Disord 2010; 25(6): 672– 678.

38. Kim TJ, Kim IO, Kim WS, Cheon JE, Moon SG, Kwon JW et al. MR imaging of the brain in Wilson disease of childhood: findings before and after treatment with clinical correlation. AJNR Am J Neuroradiol 2006; 27(6): 1373– 1378.

39. Huang CC, Chu NS. Resolution of cerebral white matter lesions following long‑term penicillamine therapy for Wilson‘s disease: report of a case. J Formos Med Assoc 1992; 91(6): 627– 629.

40. Walter U, Krolikowski K, Tarnacka B, Benecke R, Czlonkowska A, Dressler D. Sonographic detection of basal ganglia lesions in asymptomatic and symptomatic Wilson disease. Neurology 2005; 64(10): 1726– 1732.

41. Svetel M, Mijajlović M, Tomić A, Kresojević N, Pekmezović T, Kostić VS. Transcranial sonography in Wilson‘s disease. Parkinsonism Relat Disord 2012; 18(3): 234– 238.

42. Ferenci P, Caca K, Loudianos G, Mieli‑ Vergani G, Tanner S, Sternlieb I et al. Diagnosis and phenotypic classification of Wilson disease. Liver Int 2003; 23(3): 139– 142.

43. Weiss KH, Thurik F, Gotthardt DN, Schafer M, Teufel U, Wiegand F et al. Efficacy and Safety of Oral Chelators in Treatment of Patients with Wilson Disease. Clin Gastroenterol Hepatol 2013; 11(8): 1028– 1035.

44. Brewer GJ. Neurologically presenting Wilson‘s disease: epidemiology, pathophysiology and treatment. CNS Drugs 2005; 19(3): 185– 192.

45. Catana AM, Medici V. Liver transplantation for Wilson disease. World J Hepatol 2012; 4(1): 5– 10.

46. Stremmel W, Meyerrose KW, Niederau C, Hefter H,Kreuzpaintner G, Strohmeyer G. Wilson disease: clinical presentation, treatment, and survival. Ann Intern Med 1991; 115(9): 720– 726.

47. Walshe JM. Cause of death in Wilson disease. Mov Disord 2007; 22(15): 2216– 2220.

48. Brewer GJ, Terry CA, Aisen AM, Hill GM. Worsening of neurologic syndrome in patients with Wilson‘s disease with initial penicillamine therapy. Arch Neurol 1987; 44(5): 490– 493.

49. Wiggelinkhuizen M, Tilanus ME, Bollen CW, Houwen RH. Systematic review: clinical efficacy of chelator agents and zinc in the initial treatment of Wilson disease. Aliment Pharmacol Ther 2009; 29(9): 947– 958.

50. Holscher S, Leinweber B, Hefter H, Reuner U, Gunther P, Weiss KH et al. Evaluation of the symptomatic treatment of residual neurological symptoms in Wilson disease. Eur Neurol 2010; 64(2): 83– 87.

51. Walshe JM, Dixon AK. Dangers of non‑compliance in Wilson‘s disease. Lancet 1986; 1(8485): 845– 847.

52. Carta M, Mura G, Sorbello O, Farina G, Demelia L.Quality of Life and Psychiatric Symptoms in Wilson‘s Disease: the Relevance of Bipolar Disorders. Clin Pract Epidemiol Ment Health 2012; 8: 102– 109.

53. Starosta‑ Rubinstein S, Young AB, Kluin K, Hill G, Aisen AM, Gabrielsen T et al. Clinical assessment of 31 patients with Wilson‘s disease. Correlations with structural changes on magnetic resonance imaging. Arch Neurol 1987; 44(4): 365– 370.

54. Machado AA, Deguti MM, Genschel J, Cancado EL, Bochow B, Schmidt H et al. Neurological manifestations and ATP7B mutations in Wilson‘s disease. Parkinsonism Relat Disord 2008; 14(3): 246– 249.

55. Prashanth LK, Sinha S, Taly AB, Mahadevan A, Vasudev MK, Shankar SK. Spectrum of epilepsy in Wilson‘s disease with electroencephalographic, MR imaging and pathological correlates. J Neurol Sci 2010; 291(1– 2): 44– 51.