Wilson disease - Symptoms, Causes, Images, and Treatment Options

Diseases

Highlights & Basics

Key Highlights

Wilson disease is an autosomal-recessive disease of copper accumulation and toxicity caused by a defect in an enzyme involved in the excretion of excess copper.
Estimated prevalence is 1 in 30,000 to 1 in 50,000, with no sex or ethnic predominance.
Wilson disease is a systemic disease that can often mimic other conditions, commonly leading to delayed diagnosis or misdiagnosis. It should be considered in patients with abnormal liver enzymes, cirrhosis, neurologic conditions, or psychiatric disorders.
Screening and diagnostic tests: 24-hour urine copper measurement, ophthalmologic slit-lamp examination for Kayser-Fleischer (KF) rings, blood ceruloplasmin levels, serum copper, and liver biopsy with measurement of quantitative copper. If available, genetic testing for ATP7B can be done.
Treatment regimens vary depending on the clinical presentation and treatment phase (initial or maintenance). Pharmacologic therapy includes the oral chelators penicillamine (as the D-isomer) and trientine, which increase urinary copper excretion, and zinc salts, which decrease alimentary copper absorption. In certain severe hepatic cases, liver transplantation can be curative.

Eye demonstrating Kayser-Fleischer ring

Adapted from BMJ (2009); used with permission

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Images

Eye demonstrating Kayser-Fleischer ring

Citations

Key Articles

Schilsky ML, Roberts EA, Bronstein JM, et al. A multidisciplinary approach to the diagnosis and management of Wilson disease: executive summary of the 2022 practice guidance on Wilson disease from the American Association for the Study of Liver Diseases. Hepatology. 2023 Apr 1;77(4):1428-55.[Abstract][Full Text]
Shribman S, Marjot T, Sharif A, et al; British Association for the Study of the Liver Rare Diseases Special Interest Group. Investigation and management of Wilson's disease: a practical guide from the British Association for the Study of the Liver. Lancet Gastroenterol Hepatol. 2022 Jun;7(6):560-75.[Abstract]
Socha P, Janczyk W, Dhawan A, et al. Wilson's disease in children: a position paper by the Hepatology Committee of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2018 Feb;66(2):334-44.[Abstract][Full Text]
European Association for the Study of the Liver. EASL clinical practice guidelines: Wilson's disease. J Hepatol. 2012 Mar;56(3):671-85.[Abstract][Full Text]
Nazer H, Ede RJ, Mowat AP, et al. Wilson's disease: clinical presentation and use of prognostic index. Gut. 1986 Nov;27(11):1377-81.[Abstract][Full Text]

Referenced Articles

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2. 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 Dec;5(4):344-50.[Abstract]
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5. Schilsky ML, Roberts EA, Bronstein JM, et al. A multidisciplinary approach to the diagnosis and management of Wilson disease: executive summary of the 2022 practice guidance on Wilson disease from the American Association for the Study of Liver Diseases. Hepatology. 2023 Apr 1;77(4):1428-55.[Abstract][Full Text]
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17. Ferenci P, Stremmel W, Członkowska A, et al. Age and sex but not ATP7B genotype effectively influence the clinical phenotype of Wilson disease. Hepatology. 2019 Apr;69(4):1464-76.[Abstract]
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23. Socha P, Janczyk W, Dhawan A, et al. Wilson's disease in children: a position paper by the Hepatology Committee of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2018 Feb;66(2):334-44.[Abstract][Full Text]
24. Taly AB, Meenakshi-Sundaram S, Sinha S, et al. Wilson disease: description of 282 patients evaluated over 3 decades. Medicine (Baltimore). 2007 Mar;86(2):112-21.[Abstract][Full Text]
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28. Merle U, Eisenbach C, Weiss KH, et al. Serum ceruloplasmin oxidase activity is a sensitive and highly specific diagnostic marker for Wilson's disease. J Hepatol. 2009 Nov;51(5):925-30.[Abstract]
29. McMillin GA, Travis JJ, Hunt JW. Direct measurement of free copper in serum or plasma ultrafiltrate. Am J Clin Pathol. 2009 Feb;131(2):160-5.[Abstract][Full Text]
30. Stromeyer FW, Ishak KG. Histology of the liver in Wilson's disease: a study of 34 cases. Am J Clin Pathol. 1980 Jan;73(1):12-24.[Abstract]
31. Johncilla M, Mitchell KA. Pathology of the liver in copper overload. Semin Liver Dis. 2011 Aug;31(3):239-44.[Abstract]
32. van Wassenaer-van Hall HN. Neuroimaging in Wilson disease. Metab Brain Dis. 1997 Mar;12(1):1-19.[Abstract]
33. Gupta A, Chakravarthi S, Goyal MK. 'Face of giant panda': a rare imaging sign in Wilson's disease. QJM. 2014 Jul;107(7):579.[Abstract][Full Text]
34. Collins CJ, Yi F, Dayuha R, et al. Direct measurement of ATP7B peptides is highly effective in the diagnosis of Wilson disease. Gastroenterology. 2021 Jun;160(7):2367-82.e1.[Abstract][Full Text]
35. Owada M, Suzuki K, Fukushi M, et al. Mass screening for Wilson's disease by measuring urinary holoceruloplasmin. J Pediatr. 2002 May;140(5):614-6.[Abstract]
36. Aoki K. Newborn screening in Japan. Southeast Asian J Trop Med Public Health. 2003;34 Suppl 3:80.[Abstract]
37. Kroll CA, Ferber MJ, Dawson BD, et al. Retrospective determination of ceruloplasmin in newborn screening blood spots of patients with Wilson disease. Mol Genet Metab. 2006 Sep-Oct;89(1-2):134-8.[Abstract]
38. Reau N, Munoz SJ, Schiano T. Liver disease during pregnancy. Am J Gastroenterol. 2022 Oct 1;117(10s):44-52.[Abstract][Full Text]
39. American College of Radiology. ACR Appropriateness Criteria®: abnormal liver function tests. 2023 [internet publication].[Full Text]
40. Hedera P. Update on the clinical management of Wilson's disease. Appl Clin Genet. 2017 Jan 13;10:9-19.[Abstract][Full Text]
41. European Association for the Study of the Liver. EASL clinical practice guidelines: Wilson's disease. J Hepatol. 2012 Mar;56(3):671-85.[Abstract][Full Text]
42. Walshe JM. The management of Wilson's disease with trienthylene tetramine 2HC1 (Trien 2HC1). Prog Clin Biol Res. 1979;34:271-80.[Abstract]
43. Scheinberg IH, Jaffe ME, Sternlieb I. The use of trientine in preventing the effects of interrupting penicillamine therapy in Wilson's disease. N Engl J Med. 1987 Jul 23;317(4):209-13.[Abstract]
44. Ala A, Aliu E, Schilsky ML. Prospective pilot study of a single daily dosage of trientine for the treatment of Wilson disease. Dig Dis Sci. 2015 May;60(5):1433-9.[Abstract][Full Text]
45. Boga S, Jain D, Schilsky ML. Trientine induced colitis during therapy for Wilson disease: a case report and review of the literature. BMC Pharmacol Toxicol. 2015 Nov 20;16:30.[Abstract][Full Text]
46. Wiernicka A, Jańczyk W, Dądalski M, et al. Gastrointestinal side effects in children with Wilson's disease treated with zinc sulphate. World J Gastroenterol. 2013 Jul 21;19(27):4356-62.[Abstract][Full Text]
47. Czlonkowska A, Gajda J, Rodo M. Effects of long-term treatment in Wilson's disease with D-penicillamine and zinc sulphate. J Neurol. 1996 Mar;243(3):269-73.[Abstract]
48. Lang CJ, Rabas-Kolominsky P, Engelhardt A, et al. Fatal deterioration of Wilson's disease after institution of oral zinc therapy. Arch Neurol. 1993 Oct;50(10):1007-8.[Abstract]
49. Nazer H, Ede RJ, Mowat AP, et al. Wilson's disease: clinical presentation and use of prognostic index. Gut. 1986 Nov;27(11):1377-81.[Abstract][Full Text]
50. Dhawan A, Taylor RM, Cheeseman P, et al. Wilson's disease in children: 37-year experience and revised King's score for liver transplantation. Liver Transpl. 2005 Apr;11(4):441-8.[Abstract][Full Text]
51. Chanpong A, Dhawan A. Re-evaluation of King Wilson Index in children with acutely decompensated hepatic Wilson disease. J Pediatr Gastroenterol Nutr. 2022 Apr 1;74(4):510-5.[Abstract]
52. Santos Silva EE, Sarles J, Buts JP, et al. Successful medical treatment of severely decompensated Wilson disease. J Pediatr. 1996 Feb;128(2):285-7.[Abstract]
53. Pinter R, Hogge WA, McPherson E. Infant with severe penicillamine embryopathy born to a woman with Wilson disease. Am J Med Genet A. 2004 Jul 30;128A(3):294-8.[Abstract]
54. Pfeiffenberger J, Beinhardt S, Gotthardt DN, et al. Pregnancy in Wilson's disease: management and outcome. Hepatology. 2018 Apr;67(4):1261-9.[Abstract][Full Text]
55. Mussi MCL, Nardelli MJ, Santos BC, et al. Pregnancy outcomes in Wilson's disease women: single-center case series. Fetal Pediatr Pathol. 2021 Aug 5;:1-8.[Abstract]
56. Yu XE, Pan M, Han YZ, et al. The study of Wilson disease in pregnancy management. BMC Pregnancy Childbirth. 2019 Dec 26;19(1):522.[Abstract][Full Text]
57. Kodama H, Anan Y, Izumi Y, et al. Copper and zinc concentrations in the breast milk of mothers undergoing treatment for Wilson's disease: a prospective study. BMJ Paediatr Open. 2021;5(1):e000948.[Abstract][Full Text]
58. ClinicalTrials.gov. CHELATE Study: trientine tetrahydrochloride (TETA 4HCL) for the treatment of Wilson's disease. NCT03539952. Apr 2022 [internet publication].[Full Text]
59. Brewer GJ, Hedera P, Kluin KJ, et al. Treatment of Wilson disease with ammonium tetrathiomolybdate: III. Initial therapy in a total of 55 neurologically affected patients and follow-up with zinc therapy. Arch Neurol. 2003 Mar;60(3):379-85.[Abstract][Full Text]
60. Brewer GJ, Askari F, Lorincz MT, et al. Treatment of Wilson disease with ammonium tetrathiomolybdate: IV. Comparison of tetrathiomolybdate and trientine in a double-blind study of treatment of the neurologic presentation of Wilson disease. Arch Neurol. 2006 Apr;63(4):521-7.[Abstract][Full Text]
61. Brewer GJ, Terry CA, Aisen AM, et al. Worsening of neurologic syndrome in patients with Wilson's disease with initial penicillamine therapy. Arch Neurol. 1987 May;44(5):490-3.[Abstract]
62. ClinicalTrials.gov. A phase 2, single-arm pathologist-blinded 48-week study using liver biopsy specimens to assess copper concentration and histopathologic changes in ALXN1840-treated patients with Wilson disease followed by an up to 48-weeks extension period. NCT04422431. Jul 2022 [internet publication].[Full Text]
63. ClinicalTrials.gov. A phase I/II study of VTX-801 in adult patients with Wilson's disease (GATEWAY). NCT04537377. Aug 2022 [internet publication].[Full Text]
64. ClinicalTrials.gov. Clinical study of UX701 AAV-mediated gene transfer for the treatment of Wilson disease. NCT04884815. Aug 2022 [internet publication].[Full Text]
65. Askari FK, Greenson J, Dick RD, et al. Treatment of Wilson's disease with zinc. XVIII. Initial treatment of the hepatic decompensation presentation with trientine and zinc. J Lab Clin Med. 2003 Dec;142(6):385-90.[Abstract]