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Semin Neurol 2023; 43(04): 626-633
DOI: 10.1055/s-0043-1771465
Review Article

Wilson's Disease

Manida Wungjiranirun
1   Division of Gastroenterology, Department of Medicine, Oregon Health and Science University, Portland, Oregon
,
Kaveh Sharzehi
1   Division of Gastroenterology, Department of Medicine, Oregon Health and Science University, Portland, Oregon
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Abstract

Wilson's disease (WD) can present with liver disease, neurological deficits, and psychiatric disorders. Results of genetic prevalence studies suggest that WD might be much more common than previously estimated. Early recognition of WD remains challenging because it is a great imitator and requires a high index of suspicion for correct and timely diagnosis. Early diagnosis of WD is crucial to ensure that patients can be started on adequate treatment. In association with other clinical and biochemical tests, liver biopsy results and molecular genetic testing can also be used for diagnosing WD. Medical therapy is effective for most patients; liver transplant can rescue those with acute liver failure or those with advanced liver disease who fail to respond to or discontinue medical therapy. Although novel therapies, such as gene therapy, are on the horizon, screening and prevention of delayed diagnosis remains paramount.

Keywords - Wilson’s disease - acute liver failure


Publication History

Article published online:
22 August 2023

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  • References

  • 1 Wilson S. Progressive lenticular degeneration: a familial nervous disease associated with cirrhosis of the liver. Brain 1912; 34 (04) 295-507
    CrossrefPubMedGoogle Scholar
  • 2 Sternlieb I, Scheinberg IH. Prevention of Wilson's disease in asymptomatic patients. N Engl J Med 1968; 278 (07) 352-359
    CrossrefPubMedGoogle Scholar
  • 3 Scheinberg IH, Sternlieb I. Wilson's disease. In: Major Problems in Internal Medicine Series. Philadelphia: W. B. Saunders; 1984: 192
    Google Scholar
  • 4 Sandahl TD, Laursen TL, Munk DE, Vilstrup H, Weiss KH, Ott P. The prevalence of Wilson's disease: an update. Hepatology 2020; 71 (02) 722-732
    CrossrefPubMedGoogle Scholar
  • 5 Gitlin JD. Wilson disease. Gastroenterology 2003; 125 (06) 1868-1877
    CrossrefPubMedGoogle Scholar
  • 6 Ala A, Walker AP, Ashkan K, Dooley JS, Schilsky ML. Wilson's disease. Lancet 2007; 369 (9559): 397-408
    CrossrefPubMedGoogle Scholar
  • 7 Sandahl TD, Gormsen LC, Kjaergaard K. et al. The pathophysiology of Wilson's disease visualized: a human 64 Cu PET study. Hepatology 2022; 75 (06) 1461-1470
    CrossrefPubMedGoogle Scholar
  • 8 Alt ER, Sternlieb I, Goldfischer S. The cytopathology of metal overload. Int Rev Exp Pathol 1990; 31: 165-188
    CrossrefPubMedGoogle Scholar
  • 9 Müller T, Langner C, Fuchsbichler A. et al. Immunohistochemical analysis of Mallory bodies in Wilsonian and non-Wilsonian hepatic copper toxicosis. Hepatology 2004; 39 (04) 963-969
    CrossrefPubMedGoogle Scholar
  • 10 Strand S, Hofmann WJ, Grambihler A. et al. Hepatic failure and liver cell damage in acute Wilson's disease involve CD95 (APO-1/Fas) mediated apoptosis. Nat Med 1998; 4 (05) 588-593
    CrossrefPubMedGoogle Scholar
  • 11 Machado A, Chien HF, Deguti MM. et al. Neurological manifestations in Wilson's disease: report of 119 cases. Mov Disord 2006; 21 (12) 2192-2196
    CrossrefPubMedGoogle Scholar
  • 12 Pfeiffer RF. Wilson disease. Continuum (Minneap Minn) 2016; 22 (4 Movement Disorders): 1246-1261
    PubMedGoogle Scholar
  • 13 Schilsky ML, Roberts EA, Bronstein JM. et al. A multidisciplinary approach to the diagnosis and management of Wilson disease: 2022 practice guidance on Wilson disease from the American Association for the Study of Liver Diseases. Hepatology 2022; 0: 1-49
    PubMedGoogle Scholar
  • 14 Wendon J, Cordoba J, Dhawan A. et al; European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu, Clinical practice guidelines panel, Panel members, EASL Governing Board representative. EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure. J Hepatol 2017; 66 (05) 1047-1081
    CrossrefPubMedGoogle Scholar
  • 15 Ostapowicz G, Fontana RJ, Schiødt FV. et al; U.S. Acute Liver Failure Study Group. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med 2002; 137 (12) 947-954
    CrossrefPubMedGoogle Scholar
  • 16 Trey C, Davidson CS. The management of fulminant hepatic failure. Prog Liver Dis 1970; 3: 282-298
    PubMedGoogle Scholar
  • 17 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; 77 (04) 1428-1455
    CrossrefPubMedGoogle Scholar
  • 18 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 (07) 551-556
    CrossrefPubMedGoogle Scholar
  • 19 Członkowska A, Litwin T, Dzieżyc K, Karliński M, Bring J, Bjartmar C. Characteristics of a newly diagnosed Polish cohort of patients with neurological manifestations of Wilson disease evaluated with the Unified Wilson's Disease Rating Scale. BMC Neurol 2018; 18 (01) 34
    CrossrefPubMedGoogle Scholar
  • 20 Walshe JM, Yealland M. Wilson's disease: the problem of delayed diagnosis. J Neurol Neurosurg Psychiatry 1992; 55 (08) 692-696
    CrossrefPubMedGoogle Scholar
  • 21 Merle U, Schaefer M, Ferenci P, Stremmel W. Clinical presentation, diagnosis and long-term outcome of Wilson's disease: a cohort study. Gut 2007; 56 (01) 115-120
    CrossrefPubMedGoogle Scholar
  • 22 Hedera P. Wilson's disease: a master of disguise. Parkinsonism Relat Disord 2019; 59: 140-145
    CrossrefPubMedGoogle Scholar
  • 23 Pellecchia MT, Criscuolo C, Longo K, Campanella G, Filla A, Barone P. Clinical presentation and treatment of Wilson's disease: a single-centre experience. Eur Neurol 2003; 50 (01) 48-52
    CrossrefPubMedGoogle Scholar
  • 24 Starosta-Rubinstein S, Young AB, Kluin K. et al. Clinical assessment of 31 patients with Wilson's disease. Correlations with structural changes on magnetic resonance imaging. Arch Neurol 1987; 44 (04) 365-370
    CrossrefPubMedGoogle Scholar
  • 25 Oder W, Grimm G, Kollegger H, Ferenci P, Schneider B, Deecke L. Neurological and neuropsychiatric spectrum of Wilson's disease: a prospective study of 45 cases. J Neurol 1991; 238 (05) 281-287
    CrossrefPubMedGoogle Scholar
  • 26 Stremmel W, Meyerrose KW, Niederau C, Hefter H, Kreuzpaintner G, Strohmeyer G. Wilson disease: clinical presentation, treatment, and survival. Ann Intern Med 1991; 115 (09) 720-726
    CrossrefPubMedGoogle Scholar
  • 27 Soltanzadeh A, Soltanzadeh P, Nafissi S, Ghorbani A, Sikaroodi H, Lotfi J. Wilson's disease: a great masquerader. Eur Neurol 2007; 57 (02) 80-85
    CrossrefPubMedGoogle Scholar
  • 28 Mura G, Zimbrean PC, Demelia L, Carta MG. Psychiatric comorbidity in Wilson's disease. Int Rev Psychiatry 2017; 29 (05) 445-462
    CrossrefPubMedGoogle Scholar
  • 29 Dening TR, Berrios GE. Wilson's disease. Psychiatric symptoms in 195 cases. Arch Gen Psychiatry 1989; 46 (12) 1126-1134
    CrossrefPubMedGoogle Scholar
  • 30 Litwin T, Gromadzka G, Członkowska A. Gender differences in Wilson's disease. J Neurol Sci 2012; 312 (1-2): 31-35
    CrossrefPubMedGoogle Scholar
  • 31 Zimbrean PC, Schilsky ML. Psychiatric aspects of Wilson disease: a review. Gen Hosp Psychiatry 2014; 36 (01) 53-62
    CrossrefPubMedGoogle Scholar
  • 32 Kumar R, Datta S, Jayaseelan L, Gnanmuthu C, Kuruvilla K. The psychiatric aspects of Wilson's disease-a study from a neurology unit. Indian J Psychiatry 1996; 38 (04) 208-211
    PubMedGoogle Scholar
  • 33 Lowette KF, Desmet K, Witters P. et al. Wilson's disease: long-term follow-up of a cohort of 24 patients treated with D-penicillamine. Eur J Gastroenterol Hepatol 2010; 22 (05) 564-571
    CrossrefPubMedGoogle Scholar
  • 34 Srinivas K, Sinha S, Taly AB. et al. Dominant psychiatric manifestations in Wilson's disease: a diagnostic and therapeutic challenge!. J Neurol Sci 2008; 266 (1-2): 104-108
    CrossrefPubMedGoogle Scholar
  • 35 Prashanth LK, Taly AB, Sinha S, Arunodaya GR, Swamy HS. Wilson's disease: diagnostic errors and clinical implications. J Neurol Neurosurg Psychiatry 2004; 75 (06) 907-909
    CrossrefPubMedGoogle Scholar
  • 36 Lin LJ, Wang DX, Ding NN, Lin Y, Jin Y, Zheng CQ. Comprehensive analysis on clinical features of Wilson's disease: an experience over 28 years with 133 cases. Neurol Res 2014; 36 (02) 157-163
    CrossrefPubMedGoogle Scholar
  • 37 Frota NA, Barbosa ER, Porto CS. et al. Cognitive impairment and magnetic resonance imaging correlations in Wilson's disease. Acta Neurol Scand 2013; 127 (06) 391-398
    CrossrefPubMedGoogle Scholar
  • 38 Cochen De Cock V, Lacombe S, Woimant F, Poujois A. Sleep disorders in Wilson's disease. Sleep Med 2021; 83: 299-303
    CrossrefPubMedGoogle Scholar
  • 39 Tribl GG, Bor-Seng-Shu E, Trindade MC, Lucato LT, Teixeira MJ, Barbosa ER. Wilson's disease presenting as rapid eye movement sleep behavior disorder: a possible window to early treatment. Arq Neuropsiquiatr 2014; 72 (09) 653-658
    CrossrefPubMedGoogle Scholar
  • 40 Kłysz B, Bembenek J, Skowrońska M, Członkowska A, Kurkowska-Jastrzębska I. Autonomic nervous system dysfunction in Wilson's disease - a systematic literature review. Auton Neurosci 2021; 236: 102890
    CrossrefPubMedGoogle Scholar
  • 41 Meenakshi-Sundaram S, Taly AB, Kamath V, Arunodaya GR, Rao S, Swamy HS. Autonomic dysfunction in Wilson's disease –a clinical and electrophysiological study. Clin Auton Res 2002; 12 (03) 185-189
    CrossrefPubMedGoogle Scholar
  • 42 Chu EC, Chu NS, Huang CC. Autonomic involvement in Wilson's disease: a study of sympathetic skin response and RR interval variation. J Neurol Sci 1997; 149 (02) 131-137
    CrossrefPubMedGoogle Scholar
  • 43 Roberts EA, Schilsky ML. Division of Gastroenterology and Nutrition, Hospital for Sick Children, Toronto, Ontario, Canada. A practice guideline on Wilson disease. Hepatology 2003; 37 (06) 1475-1492
    CrossrefPubMedGoogle Scholar
  • 44 Quemeneur AS, Trocello JM, Ea HK. et al. Bone status and fractures in 85 adults with Wilson's disease. Osteoporos Int 2014; 25 (11) 2573-2580
    CrossrefPubMedGoogle Scholar
  • 45 Shah R, Amador C, Tormanen K. et al. Systemic diseases and the cornea. Exp Eye Res 2021; 204: 108455
    CrossrefPubMedGoogle Scholar
  • 46 Jang HJ, Kim JM, Choi CY. Elemental analysis of sunflower cataract in Wilson's disease: a study using scanning transmission electron microscopy and energy dispersive spectroscopy. Exp Eye Res 2014; 121: 58-65
    CrossrefPubMedGoogle Scholar
  • 47 Mezaki T, Matsumoto S, Hamada C. et al. Decreased serum ceruloplasmin and copper levels in cervical dystonia. Ann Neurol 2001; 49 (01) 138-139
    CrossrefPubMedGoogle Scholar
  • 48 Korman JD, Volenberg I, Balko J. et al; Pediatric and Adult Acute Liver Failure Study Groups. Screening for Wilson disease in acute liver failure: a comparison of currently available diagnostic tests. Hepatology 2008; 48 (04) 1167-1174
    CrossrefPubMedGoogle Scholar
  • 49 Tu JB, Blackwell RQ. Studies on levels of penicillamine-induced cupriuresis in heterozygotes of Wilson's disease. Metabolism 1967; 16 (06) 507-513
    CrossrefPubMedGoogle Scholar
  • 50 Mounajjed T, Oxentenko AS, Qureshi H, Smyrk TC. Revisiting the topic of histochemically detectable copper in various liver diseases with special focus on venous outflow impairment. Am J Clin Pathol 2013; 139 (01) 79-86
    CrossrefPubMedGoogle Scholar
  • 51 EASL Clinical Practice Guidelines: Wilson's disease. J Hepatol 2012; 56 (03) 671-685
    CrossrefPubMedGoogle Scholar
  • 52 Saroli Palumbo C, Schilsky ML. Clinical practice guidelines in Wilson disease. Ann Transl Med 2019; 7 (Suppl. 02) S65
    CrossrefPubMedGoogle Scholar
  • 53 Ferenci P, Caca K, Loudianos G. et al. Diagnosis and phenotypic classification of Wilson disease. Liver Int 2003; 23 (03) 139-142
    CrossrefPubMedGoogle Scholar
  • 54 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; 317 (04) 209-213
    CrossrefPubMedGoogle Scholar
  • 55 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; 16: 30
    CrossrefPubMedGoogle Scholar
  • 56 Rodriguez-Castro KI, Hevia-Urrutia FJ, Sturniolo GC. Wilson's disease: a review of what we have learned. World J Hepatol 2015; 7 (29) 2859-2870
    CrossrefPubMedGoogle Scholar
  • 57 Weiss KH, Schäfer M, Gotthardt DN. et al. Outcome and development of symptoms after orthotopic liver transplantation for Wilson disease. Clin Transplant 2013; 27 (06) 914-922
    CrossrefPubMedGoogle Scholar
  • 58 Poujois A, Sobesky R, Meissner WG. et al. Liver transplantation as a rescue therapy for severe neurologic forms of Wilson disease. Neurology 2020; 94 (21) e2189-e2202
    CrossrefPubMedGoogle Scholar
  • 59 Allocca S, Ciano M, Ciardulli MC. et al. An αB-crystallin peptide rescues compartmentalization and trafficking response to Cu overload of ATP7B-H1069Q, the most frequent cause of Wilson disease in the Caucasian population. Int J Mol Sci 2018; 19 (07) 1892
    CrossrefPubMedGoogle Scholar
  • 60 Murillo O, Luqui DM, Gazquez C. et al. Long-term metabolic correction of Wilson's disease in a murine model by gene therapy. J Hepatol 2016; 64 (02) 419-426
    CrossrefPubMedGoogle Scholar
  • 61 Beinhardt S, Leiss W, Stättermayer AF. et al. Long-term outcomes of patients with Wilson disease in a large Austrian cohort. Clin Gastroenterol Hepatol 2014; 12 (04) 683-689
    CrossrefPubMedGoogle Scholar
  • 62 Dzieżyc K, Karliński M, Litwin T, Członkowska A. Compliant treatment with anti-copper agents prevents clinically overt Wilson's disease in pre-symptomatic patients. Eur J Neurol 2014; 21 (02) 332-337
    CrossrefPubMedGoogle Scholar
  • 63 Schilsky ML, Scheinberg IH, Sternlieb I. Prognosis of Wilsonian chronic active hepatitis. Gastroenterology 1991; 100 (03) 762-767
    CrossrefPubMedGoogle Scholar
  • 64 Akil M, Schwartz JA, Dutchak D, Yuzbasiyan-Gurkan V, Brewer GJ. The psychiatric presentations of Wilson's disease. J Neuropsychiatry Clin Neurosci 1991; 3 (04) 377-382
    CrossrefPubMedGoogle Scholar