Abstract
Wilson’s disease is an autosomal recessive disorder due to inheritance of two mutant alleles of a putative copper transporter (ATP7B) encoded by a gene on chromosome 13 (1– 5). Biliary copper excretion is reduced resulting in the accumulation of copper, first in the liver and later in other organs of homozygotes (6, 7). The abnormal accumulation of copper results initially in liver injury, followed by accumulation of copper in the brain, kidneys, and in other organs. The condition of the liver to the injury is determined by a balance between cell death, inflammation and regeneration. When cell death is overwhelming, fulminant hepatitis results. Most often, cell injury and inflammatory changes are chronic, leading to fibrosis and cirrhosis. Unless treated, liver disease progresses to hepatic insufficiency and death. Individuals who are heterozygous for the Wilson’s disease mutation may manifest minor abnormalities in copper metabolism, but do not develop the disease and do not require treatment (8).
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Frydman M, Bonne-Tammir B, Fairer LA, Conneally PM, Magazanik A, Ashbel S, Goldwitch Z. Assignment of the gene for Wilson disease to chromosome 13: linkage to the esterase D locus. Proc Natl Acad Sci USA 1985;82:1819–1821.
Tanzi RE, Petrukhin K, Chernov I, Pellequer JL, et al. The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene. Nat Genet 1993;5:344–350.
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;5:327–337.
Yamaguchi Y, Heiny ME, Gitlin JD. Isolation and characterization of a human liver cDNA as a candidate gene for Wilson disease. Biochem Biophys Res Commun 1993; 197:271–277.
Petrukhin K, Lutsenko S, Chernov I, Ross BM, Kaplan JH, Gilliam TC. Characterization of the Wilson disease gene encoding a P-type copper transporting ATPase: genomic organization, alternative splicing, and structure/ function predictions. Hum Mol Genet 1994;3:1647–1656.
Frommer DJ. Defective biliary excretion of copper in Wilson’s disease. Gut 1974;15:125–129.
Sternlieb I, van den Hamer CJA, Morell AG, Alpert S, Gregoriadis G, Scheinberg IH. Lysosomal defect of hepatic copper excretion in Wilson’s disease (hepatolenticular degeneration). Gastroenterology 1973;64:99–105.
Scheinberg IH, Sternlieb I. Wilson’s disease. Saunders, Philadelphia, 1984.
Alt E, Sternlieb I, Goldfischer S. The cytopathology of metal overload [review]. Int Rev Exp Pathol 1990;31:165–188.
Sternlieb I. Mitochondrial and fatty changes in hepatocytes of patients with Wilson’s disease. Gastroenterology 1968;55:354–367.
Sternlieb I. Fraternal concordance of types of abnormal hepatocellular mitochondria in Wilson’s disease. Hepatology 1992; 16:728–732.
Schilsky ML, Scheinberg IH, Sternlieb I. Liver transplantation for Wilson’s disease: indications and outcome. Hepatology 1994; 19:583–587.
Shaver WA, Bhatt H, Combes B. Low serum alkaline phosphatase activity in Wilson’s disease. Hepatology 1986;6:859–863.
Wilson RA, Clayson KJ, Leon S. Unmeasurable serum alkaline phosphatase activity in Wilson’s disease associated with fulminant hepatic failure and hemolysis. Hepatology 1987;7:613–615.
McCullough AJ, Fleming CR, Thistle JL, Baldus WP, Ludwig J, McCall JT, Dickson ER. Diagnosis of Wilson’s disease presenting as fulminant hepatic failure. Gastroenterology 1983;84:161–167.
Berman DH, Leventhal RI, Gavaler JS, Cadoff EM, Van Thiel DH. Clinical differentiation of fulminant Wilsonian hepatitis from other causes of hepatic failure. Gastroenterology 1991;100:1129–1134.
Sallie R, Katsiyiannakis L, Baldwin D, et al. Failure of simple biochemical indexes to reliably differentiate fulminant Wilson’s disease from other causes of fulminant liver failure. Hepatology 1992; 16:1206–1211.
Schilsky ML, Scheinberg IH, Sternlieb I. Prognosis of Wilsonian chronic active hepatitis. Gastroenterology 1991; 100:762–767.
Walshe JM, Yealland M. Chelational treatment of neurological Wilson’s disease. Q J Med 1993;86:197–204.
Starosta-Rubinstein S, Young AB, Kluin K, Hill G, Aisen AM, Gabreilsen T, Brewer GJ. Clinical assessment of 31 patients with Wilson’s disease: Correlations with structural changes on magnetic resonance imaging. Arch Neurol 1987;44:365–370.
van Wassenaer-van Hall HN, van den Heuvel AG, Algra A, et al. Wilson disease: findings at MR imaging and CT of the brain with clinical correlation. Radiology 1996;198:531–536.
Petrukhin K, Fischer SG, Pirastu M, et al. Mapping, cloning and genetic characterization of the region containing the Wilson disease gene. Nat Gen 1993;5:338–343.
Walshe JM. Copper chelation in Wilson’s disease. A comparison of penicillamine and triethylene tetramine dihydrochloride. Q J Med 1973;42:441–452.
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;317:209–213.
Scheinberg IH, Sternlieb I. Treatment of the neurologic manifestations of Wilson’s disease. Arch Neurol 1994;51:545–554.
Brewer GJ, Dick RD, Yuzbasiyan-Gurkan V, Johnson V, Wang Y. Treatment of Wilson’s disease with zinc XIII. Therapy with zinc in presymptomatic patients from the time of diagnosis. J Lab Clin Med 1994; 123:849–858.
Cousins RJ. Absorption, transport, and hepatic metabolism of copper and zinc: special reference to metallothionein and ceruloplasmin. Physiol Rev 1985;65:238–309.
Collins JC, Scheinberg IH, Sternlieb I. Penicillamine prophylaxis for asymptomatic children with Wilson’s disease. Hepatology 1993;18:128A.
Hoogenraad TU, Koevoet R, de Ruyter Korver EG. Oral zinc sulfate as long-term treatment in Wilson’s disease (hepatolenticular degeneration). Eur Neurol 1979; 18:205–211.
Walshe JM. Pregnancy in Wilson’s disease. Q J Med 1977; 181:73–83.
Walshe JM. The management of pregnancy in Wilson’s disease treated with trientine. Q J Med 1986;58:8–87.
Brewer JB, Yuzbasiyan-Gurkan V. Wilson’s disease. Medicine 1992;71:139–163.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1998 Springer Science+Business Media New York
About this chapter
Cite this chapter
Schilsky, M.L., Sternlieb, I. (1998). Wilson’s Disease. In: Wu, G.Y., Israel, J. (eds) Diseases of the Liver and Bile Ducts. Current Clinical Practice. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-4612-1808-1_21
Download citation
DOI: https://doi.org/10.1007/978-1-4612-1808-1_21
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-4612-7293-9
Online ISBN: 978-1-4612-1808-1
eBook Packages: Springer Book Archive