Wilson’s Disease

  • George J. BrewerEmail author
Part of the Current Clinical Neurology book series (CCNEU)


Wilson’s disease is a rare disorder with protean clinical manifestations. The diagnosis of Wilson’s disease is an emergency, because of the serious sequelae of a missed or delayed diagnosis, and because of the risk of permanent neurologic harm if the patient is mismanaged. With adequate clinical suspicion and careful application of anticopper strategies, most patients with Wilson’s disease can expect to lead a normal life.


Essential Tremor Urine Copper Urine Zinc Neurological Presentation Zinc Therapy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Supplementary material (121,410) KB


  1. 1.
    Wilson SAK. Progressive lenticular degeneration: a familial nervous disease associated with cirrhosis of the liver. Brain. 1912;34:295–509.CrossRefGoogle Scholar
  2. 2.
    Kayser B. Ueber einen Fall von angeborener grunlicher Vertarbung der korne. Klin Mbl Augenheilk. 1902;40:22–5.Google Scholar
  3. 3.
    Fleischer B. Zwei weitere Falle von grunliche Verfarbung der Korne. Klin Mbl Augenheilk. 1903;41:489–91.Google Scholar
  4. 4.
    Glazebrook AJ. Wilson’s disease. Edinburgh Med J. 1945;52:83–7.Google Scholar
  5. 5.
    Cumings JN. The copper and iron content of brain and liver in the normal and in hepato-­lenticular degeneration. Brain. 1948;71:410–5.PubMedCrossRefGoogle Scholar
  6. 6.
    Mandelbrote BM, Stanier MW, Thompson RHS, Thruston MN. Studies on copper metabolism in demyelinating disease of the central nervous system. Brain. 1948;71:212–28.PubMedCrossRefGoogle Scholar
  7. 7.
    Ravestyn AM. Metabolism of copper in man. Acta Med Scand. 1944;118:163–96.CrossRefGoogle Scholar
  8. 8.
    Frommer DJ. Defective biliary excretion of copper in Wilson’s disease. Gut. 1974;15:125–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Bearn AG, Kunkel HG. Biochemical abnormalities in Wilson’s disease. J Clin Invest. 1952;31:616.Google Scholar
  10. 10.
    Scheinberg IH, Gitlin D. Deficiency of ceruloplasmin in patients with hepatolenticular ­degeneration (Wilson’s disease). Science. 1952;116:484–5.PubMedCrossRefGoogle Scholar
  11. 11.
    Cummings JN. The effects of BAL in hepatolenticular degeneration. Brain. 1951;74:10–22.CrossRefGoogle Scholar
  12. 12.
    Walshe JM. Penicillamine: a new oral therapy for Wilson’s disease. Am J Med. 1956;21:487–95.PubMedCrossRefGoogle Scholar
  13. 13.
    Walshe JM. Treatment of Wilson’s disease with trientine (triethylene tetramine) dihydrochloride. Lancet. 1982;1:643–7.PubMedCrossRefGoogle Scholar
  14. 14.
    Schouwink G. De hepatocerebrale degeratie, me een onderzoek naar de zinktowisseling. MD Thesis, University of Amsterdam; 1961.Google Scholar
  15. 15.
    Brewer GJ, Hill GM, Prasad AS, Cossack ZT, Rabbam P. Oral zinc therapy for Wilson’s disease. Ann Intern Med. 1983;99:314–20.PubMedGoogle Scholar
  16. 16.
    Brewer GJ, Dick RD, Johnson VD, Brunberg JA, Klum KJ, Fink JK. The treatment of Wilson’s disease with zinc XV: long-term follow-up studies. J Lab Clin Med. 1998;132:264–78.PubMedCrossRefGoogle Scholar
  17. 17.
    Brewer GJ, Dick RD, Yuzbasiyan-Gurkan V, Tanakow R, Young AB, Kluin KJ. Initial therapy of patients with Wilson’s disease with tetrathiomolybdate. Arch Neurol. 1991;48:42–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Brewer GJ, Hedera P, Kluin KJ, et al. Treatment of Wilson’s disease with tetrathiomolybdate III: initial therapy in a total of 55 neurologically affected patients and follow-up with zinc therapy. Arch Neurol. 2003;60:379–85.PubMedCrossRefGoogle Scholar
  19. 19.
    Bearn AG. A genetical analysis of thirty families with Wilson’s disease (hepatolenticular degeneration). Ann Hum Genet. 1960;24:33–43.PubMedCrossRefGoogle Scholar
  20. 20.
    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 Menke’s gene. Nat Genet. 1993;5:327–37.PubMedCrossRefGoogle Scholar
  21. 21.
    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;5:44–50.CrossRefGoogle Scholar
  22. 22.
    Yamaguchi Y, Heiny ME, Gitlin JD. Isolation and characterization of a human liver cDNA as a candidate gene for Wilson disease. Biochem Biophy Res Commun. 1993;197:271–7.CrossRefGoogle Scholar
  23. 23.
    Vulpe C, Levinson B, Whitney S, Packman S, Gitschier J. Isolation of a candidate gene for Menkes disease and evidence that it encodes a copper-transporting ATP-ase. Nat Genet. 1993;3:7–13.PubMedCrossRefGoogle Scholar
  24. 24.
    Chelly J, Turner Z, Tonnesen T, et al. Isolation of a candidate gene for Menkes disease that encodes a potentially heavy metal binding protein. Nat Genet. 1993;3:14–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Mercer JF, Livingston J, Hall B, et al. Isolation of a partial candidate gene for Menkes disease by positional cloning. Nat Genet. 1993;3:20–5.PubMedCrossRefGoogle Scholar
  26. 26.
    Cox DW, Roberts EA. Wilson disease. GeneClinics, University of Washington, Seattle.
  27. 27.
    Brewer GJ, Yuzbasiyan-Gurkan V. Wilson disease. Medicine. 1992;71:139–64.PubMedCrossRefGoogle Scholar
  28. 28.
    Scheinberg IH, Sternlieb I. Wilson’s disease. In: Smith Jr LH, editor. Major problems in internal medicine, vol. 23. Philadelphia: W.B. Saunders; 1984.Google Scholar
  29. 29.
    Brewer GJ. Recognition, diagnosis and management of Wilson’s disease. Proc Soc Exp Biol Med. 2000;223:39–49.PubMedCrossRefGoogle Scholar
  30. 30.
    Brewer GJ. Wilson’s disease: a clinician’s guide to recognition, diagnosis, and management. Boston: Kluwer; 2001.Google Scholar
  31. 31.
    Brewer GJ. Wilson’s disease. In: Kasper DL, Braunwald E, Fuci AS, et al., editors. Harrison’s principles of internal medicine. New York: McGraw-Hill; 2004.Google Scholar
  32. 32.
    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;44:490–3.PubMedCrossRefGoogle Scholar
  33. 33.
    Brewer GJ, Askari F, Lorinez MT, et al. Treatment of Wilson’s disease with tetrathiomolybdate: IV Comparison of tetrathiomolybdate and trientine in a double-blind study of treatment of the neurologic presentation of Wilson’s disease. Arch Neurol. 2006;63:521–7.PubMedCrossRefGoogle Scholar
  34. 34.
    Yuzbastyan-Gurkan V, Grider A, Nostrant T, Cousins RJ, Brewer GJ. The treatment of Wilson’s disease with zinc: X Intestinal metallothionein induction. J Lab Clin Med. 1992;120:380–6.Google Scholar
  35. 35.
    Askari FK, Greenson J, Dick RD, Johnson VD, Brewer GJ. Treatment of Wilson’s disease with zinc. XVIII Initial treatment of the hepatic decompensation presentation with trientine and zinc. J Lab Clin Med. 2003;142:385–90.PubMedCrossRefGoogle Scholar
  36. 36.
    Brewer GJ, Dick RD, Johnson V, et al. Treatment of Wilson’s disease with tetrathiomolybdate; I. Initial therapy in 17 neurologically affected patients. Arch Neurol. 1994;51:545–54.PubMedCrossRefGoogle Scholar
  37. 37.
    Brewer GJ, Johnson V, Dick RD, Kluin KJ, Fink JK, Brunberg JA. Treatment of Wilson’s disease with ammonium tetrathiomolybdate; II. Initial therapy in 33 neurologically affected patients and follow-up on zinc therapy. Arch Neurol. 1996;53:1017–25.PubMedCrossRefGoogle Scholar
  38. 38.
    Brewer GJ, Askam F, Dick RB, et al. Treatment of Wilson’s disease with tetrathiomolybdate: V. Control of free copper by tetrathiomolybdate and a comparison with trientine. Transl Res. 2009;154:70–7.PubMedCrossRefGoogle Scholar
  39. 39.
    Fink JK, Hedera P, Brewer GJ. Hepatolenticular degeneration (Wilson’s disease). Neurologist. 1999;5:171–85.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Human Genetics and Internal MedicineUniversity of Michigan Medical SchoolAnn ArborUSA

Personalised recommendations