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Chapter 28 - Copper Metabolism and Copper Storage Disorders in Children

from Section IV - Metabolic Liver Disease

Published online by Cambridge University Press:  19 January 2021

By
Ronald J. Sokol  and
Arnold Silverman
Edited by
Frederick J. Suchy ,
Ronald J. Sokol  and
William F. Balistreri
Edited in association with
Jorge A. Bezerra ,
Cara L. Mack  and
Benjamin L. Shneider
Frederick J. Suchy
Affiliation:
University of Colorado, Children’s Hospital Colorado, Aurora
Ronald J. Sokol
Affiliation:
University of Colorado, Children’s Hospital Colorado, Aurora
William F. Balistreri
Affiliation:
Cincinnati Children’s Hospital Medical Center, Cincinnati
Jorge A. Bezerra
Affiliation:
Cincinnati Children’s Hospital Medical Center, Cincinnati
Cara L. Mack
Affiliation:
University of Colorado, Children’s Hospital Colorado, Aurora
Benjamin L. Shneider
Affiliation:
Texas Children’s Hospital, Houston
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Summary

Excess copper in the liver is toxic in humans and other mammals, and may lead to acute or chronic hepatitis, steatohepatitis, acute liver failure, cirrhosis and death. Of the several human copper storage diseases that have been described, the molecular basis of only Wilson disease is understood with the discovery of the Wilson disease gene (ATP7B) in 1993. The therapeutic success using oral copper chelating agents and zinc therapy make Wilson disease one of the few treatable genetic metabolic liver diseases. In cases with a fulminant presentation or advanced disease at diagnosis, copper chelation is ineffective and liver transplantation may be lifesaving. Indian Childhood Cirrhosis (ICC) has been defined as a copper-storage disorder precipitated by increased copper intake which affects young children primarily of Indian descent, and which progresses to cirrhosis and death before age three to four years without treatment. Children from North America, Asia, Austria, Germany and other countries have been described with a similar condition, which has been termed idiopathic copper toxicosis (ICT). Several newer disorders of hepatic copper metabolism have been recently described.

Type
Chapter
Information
Liver Disease in Children , pp. 484 - 514
Publisher: Cambridge University Press
Print publication year: 2021

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References

References

Czlonkowska, A, Litwin, T, Dusek, P, et al. Wilson disease. Nat Rev Disease Primers 2018;4:21.Google Scholar
Gollan, JL. Studies on the nature of complexes formed by copper with human alimentary secretions and their influence on copper absorption in the rat. Clin Sci Mol Med 1975;49:237.Google Scholar
Klomp, LW, Liu, SJ, Yuan, DS, et al. Identification and functional expression of HAH1, a novel human gene involved in copper homeostasis. J Biol Chem 1997;272:9221–6.Google Scholar
Harrison, MD, Jones, CE, Dameron, CT. Copper chaperones: function, structure and copper-binding properties. J Biol Inorg Chem 1999;4:145–53.Google Scholar
Portnoy, ME, Rosenzweig, AC, Roe, T, et al. Structure-function analyses of the ATX1 metallochaperone. J Biol Chem 1999;274:15041–5.Google Scholar
Sternlieb, I, Morell, AG, Tucker, WD, et al. The incorporation of copper into ceruloplasmin in vivo: studies with copper 64 and copper 67. J Clin Invest 1961;40:1834.CrossRefGoogle Scholar
Miyajima, H. Aceruloplasminemia: an iron metabolic disorder. Neuropathology 2003;23:345–50.CrossRefGoogle ScholarPubMed
Frieden, E, Hsieh, HS. The biological role of ceruloplasmin and its oxidase activity. Adv Exp Med Biol 1976;74:505.Google Scholar
Scheinberg, IH, Cook, CD, Murphy, JA. The concentration of copper and ceruloplasmin in maternal and infant plasma at delivery. J Clin Invest 1954;33:963.Google Scholar
Schilsky, ML, Sternlieb, I. Overcoming obstacles to the diagnosis of Wilson’s disease. Gastroenterology 1997;113:350–3.Google Scholar
Rosencrantz, R, Schilsky, M. Wilson disease: pathogenesis and clinical considerations in diagnosis and treatment. Sem Liver Disease 2011;31:245–59.CrossRefGoogle ScholarPubMed
Frommer, DJ. Defective biliary excretion of copper in Wilson’s disease. Gut 1974;15:125.Google Scholar
Mueller, T, Van de Sluis, B, Zhernakova, A, et al. The canine copper toxicosis gene MURR1 does not cause non-Wilsonian hepatic copper toxicosis. J Hepatol 2003;38:164–8.Google Scholar
Tao, TY, Liu, F, Klomp, L, et al. The copper toxicosis gene product Murr1 directly interacts with the Wilson disease protein. J Biol Chem 2003;278:41593–6.Google Scholar
Stuehler, B, Reichert, J, Stemmel, W, Schaefer, M. .Analysis of the human homologue of the canine copper toxicosis gene MURR1 in Wilson disease patients. J Mol Med 2004;82:629–6.Google Scholar
Evans, GW. Copper homeostasis in the mammalian system. Physiol Rev 1973;53:535.Google Scholar
Reed, GB, Butt, EM, Landing, BH. Copper in childhood liver disease. A histologic, histochemical and chemical survey. Arch Pathol 1972;93:249.Google ScholarPubMed
Sokol, RJ, Twedt, D, McKim, JM Jr, et al. Oxidant injury to hepatic mitochondria in patients with Wilson’s disease and Bedlington terriers with copper toxicosis. Gastroenterology 1994;107:1788–98.Google Scholar
Valko, M, Morris, H, Cronin, MT. Metals, toxicity and oxidative stress. Curr Med Chem 2005;12(10):1161–208.CrossRefGoogle ScholarPubMed
Mufti, AR, Burstein, E, Csomos, RA, et al. XIAP is a copper binding protein deregulated in Wilson’s disease and other copper toxicosis disorders. Mol Cell 2006;21(6):775–85.CrossRefGoogle ScholarPubMed
Sokol, RJ. Abnormal hepatic mitochondrial respiration and cytochrome C oxidase activity in rats with copper overload. Gastroenterology 1993;105:178–87.CrossRefGoogle ScholarPubMed
Mansouri, A, Gaou, I, Fromenty, B, et al. Premature oxidative aging of hepatic mitochondrial DNA in Wilson’s disease. Gastroenterology 1997;113:599–605.Google Scholar
Wilson, AK. Progressive lenticular degeneration: a familial nervous disease associated with cirrhosis of the liver. Brain 1912;34:295.Google Scholar
Bull, PC, Thomas, GR, Rommens, JM, et al. The Wilson’s disease gene is a putative copper transporting P-type ATPase similar to the Menkes’ gene. Nat Genet 1993;5:327–37.Google Scholar
Wilson, DC, Phillips, MJ, Cox, DW, Roberts, EA. Severe hepatic Wilson’s disease in preschool-aged children. J Pediatr 2000;137:719–22.CrossRefGoogle ScholarPubMed
Walshe, JM. (1982). The liver in Wilson’s disease (hepatolenticular degeneration). In: Schiff, L, Schiff, ER, (Eds.), Diseases of the Liver (pp. 1037–50). Philadelphia: JB Lippincott.Google Scholar
Scheinberg, IH, Sternlieb, I, (Eds.). (1984). Wilson’s disease. Philadelphia: WB Saunders.Google Scholar
Schilsky, ML, Scheinberg, IH, Sternlieb, I. Prognosis of Wilsonian chronic active hepatitis. Gastroenterology 1991;100:762–7.Google Scholar
Walshe, JM, Waldenstrom, E, Sams, V, Nordlinder, H, Westermark, K. Abdominal malignancies in patients with Wilson’s disease. QJM 2003;96:657–62.Google Scholar
Factor, SM, Cho, S, Sternlieb, I, et al. The cardiomyopathy of Wilson’s disease. Myocardial alterations in nine cases. Virchows Arch [A] 1982;397:301–11.Google Scholar
Korman, JD, Volenberg, I, Balko, J, Webster, J, Schiodt, FV, Squires, RH Jr, Fontana, RJ, Lee, WM, Schilsky, ML. 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;48:1168–74.CrossRefGoogle ScholarPubMed
Ferenci, P, Caca, K, Loudianos, G, Mieli-Vergani, G, Tanner, S, Sternlieb, I, Schilsky, M, Cox, D, Berr, F. Diagnosis and phenotypic classification of Wilson disease. Liver Int 2003;23:139–42.Google Scholar
DaCosta, CM, Baldwin, D, Portmann, B, et al. Value of urinary copper excretion after penicillamine challenge in the diagnosis of Wilson’s disease. Hepatology 1992;15:609–15.Google Scholar
Steindl, P, Ferenci, P, Dienes, HP, et al. Wilson’s disease in patients presenting with liver disease: a diagnostic challenge. Gastroenterology 1997;113:212–18.Google Scholar
Sternlieb, I. Mitochondrial and fatty changes in hepatocytes of patients with Wilson’s disease. Gastroenterology 1968;55:354.Google Scholar
Williams, FJB, Walshe, JM. Wilson’s disease. An analysis of the cranial computerized tomographic appearances found in 60 patients and the changes in response to treatment with chelating agents. Brain 1981;104:735–52.Google Scholar
Linne, T, Agartz, I, Saaf, J, et al. Cerebral abnormalities in Wilson disease as evaluated by ultra-low-field magnetic resonance imaging and computerized image processing. Magn Reson Imaging 1990;8:819–24.CrossRefGoogle ScholarPubMed
Brewer, GJ, Askari, F, Lorincz, MT, Carlson, M, Schilsky, M, Kluin, KJ, Hedera, P, Moretti, P, Fink, JK, Tankanow, R, Dick, RB, Sitterly, J. 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;63(4):521–7.CrossRefGoogle Scholar
Walshe, JM. Penicillamine, a new oral therapy for Wilson’s disease. Am J Med 1956;21:487–95.Google Scholar
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.Google Scholar
Weiss, KH, Czlonkowska, A, Hedera, P, Ferenci, P. WTX1010 – an investigational drug for the treatment of Wilson Disease. Expert Opin Invest Drugs 2018;27:561–7.Google Scholar
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;66(2):334–44.Google Scholar
Santiago, R, Gottrand, F, Debray, D, Bridoux, L, Lachaux, A, Morali, A, Lapeyre, D, Lamireau, T. Zinc therapy for Wilson disease in children in French pediatric centers. J Pediatr Gastroenterol Nutr 2015;61(6):613–18.CrossRefGoogle ScholarPubMed
Weiss, KH, Gotthardt, DN, Klemm, D, Merle, U, Ferenci-Foerster, D, Schaefer, M, Ferenci, P, Stremmel, W. Zinc monotherapy is not as effective as chelating agents in treatment of Wilson disease. Gastroenterology 2011;140(4):1189–98.Google Scholar
Garoufalia, Z, Prodromidou, A, Machairas, N, Kostakis, ID, Stamopoulos, P, Zavras, N, Fouzas, sI, Sotiropoulos, GC. Liver transplantation for Wilson’s disease in non-adult patients: a systematic review. Transplant Proc 2019;51(2):443–5.CrossRefGoogle ScholarPubMed
Nazer, H, Ede, RJ, Mowat, AP, et al. Wilson’s disease: clinical presentation and use of prognostic index. Gut 1986;27:1377–81.CrossRefGoogle ScholarPubMed
Dhawan, A, Taylor, RM, Cheeseman, P, De Silva, P, et al. Wilson’s disease in children: 37-year experience and revised King’s score for liver transplantation. Liver Transplantation 2005;11:441–8.CrossRefGoogle ScholarPubMed
Sternlieb, I. Wilson’s disease and pregnancy. Hepatology 2000;31:531–2.CrossRefGoogle ScholarPubMed
Tanner, MS. Role of copper in Indian childhood cirrhosis. Am J Clin Nutr 1998;67(suppl):1074–81.Google Scholar
Müller, T, Feichtinger, H, Berger, H, et al. Endemic Tyrolean infantile cirrhosis: an ecogenetic disorder. Lancet 1996;347:877–80.Google Scholar
O’Neill, NC, Tanner, MS. Uptake of copper from brass vessels by bovine milk and its relevance to Indian childhood cirrhosis. J Pediatr Gastroenterol Nutr 1989;9:167–72.Google Scholar
Nayak, NC, Chitale, AR. Indian Childhood cirrhosis (ICC) & ICC-like diseases: the changing scenario of facts versus notions. Indian J Med Res 2013;137:1029–42.Google ScholarPubMed
Bhave, SA, Pandit, AN, Pradhan, AM, et al. Liver disease in India. Arch Dis Child 1982;57:922.Google Scholar
Tanner, MS, Bhave, SA, Pradham, AM, et al. Clinical trials of penicillamine in Indian childhood cirrhosis. Arch Dis Child 1987;62:1118–24.Google Scholar
Horslen, SP, Tanner, MS, Lyon, TDB, et al. Copper associated childhood cirrhosis. Gut 1994;35:1497–500.Google Scholar
Scheinberg, IH, Sternlieb, I. Is non-Indian childhood cirrhosis caused by excess dietary copper. Lancet 1994;344:1002–4.Google Scholar
Saito, T. Presenting symptoms and natural history of Wilson’s disease. Eur J Pediatr 1987;146:261–5.Google Scholar
Giagheddu, A, Demelisa, L, Puggioni, G, Nurchi, AM, Contu, L, Pirari, G, Deplano, A, Rachele, MG. Epidemiologic study of hepatolenticular degeneration (Wilson’s disease) in Sardinia (1902–1983). Acta Neurol Scand 1985;72:43–55.Google Scholar
Dobyns, WB, Goldstein, NP, Gordon, H. Clinical spectrum of Wilson’s disease (hepatolenticular degeneration). Mayo Clin Proc 1979;54:35–42.Google Scholar
Stremmel, W, Meyerrose, KW, Niederau, C, et al. Wilson’s disease: clinical presentation, treatment and survival. Ann Intern Med 1991;115:720–6.Google Scholar
Aksoy, M, Erdem, S. Wilson’s disease in Turkey, a review of 49 cases in 41 families. New Istanbul Contrib Clin Sci 1975;11:92–7.Google Scholar
Oder, W, Grimm, G, Kollegger, H, et al. Neurological and neuropsychiatric spectrum of Wilson’s disease: a prospective study of 45 cases. J Neurol 1991;238:281–7.Google Scholar
Park, RHR, McCabe, P, Fell, GS, et al. Wilson’s disease in Scotland. Gut 1991;32:1541–5.Google Scholar
Martinelli, D, Dionisi-Vici, C. AP1S1 defect causing MEDNIK syndrome: a new adaptinopathy associated with defective copper metabolism. Ann N Y Acad Sci 2014;1314:55–63.Google Scholar
Martinelli, D, Travaglini, L, Drouin, CA, et al. MEDNIK syndrome: a novel defect of copper metabolism treatable by zinc acetate therapy. Brain 2013;136(Pt 3):872–81.Google Scholar
Ranucci, G, Iorio, R. (2019). Disorders that mimic Wilson disease. In: Kerkar, N, Roberts, EA (Eds.). Clinical and translational perspectives on Wilson disease (pp. 419–25). London: Academic Press, Elsevier.Google Scholar
Shneider, BL. ABCB4 disease presenting with cirrhosis and copper overload- potential confusion with Wilson disease. J Clin Exp Hepatol 2011;1:115–227.CrossRefGoogle ScholarPubMed

Websites of Interest

GeneReviews – Wilson Disease: www.ncbi.nlm.nih.gov/books/NBK1512/ [last accessed June 21, 2020].

Wilson Disease Association: www.wilsonsdisease.org/ [last accessed June 21, 2020].

National Organization for Rare Disorders: https://rarediseases.org/rare-diseases/wilson-disease/ [last accessed June 21, 2020].

Genetics and Rare Disease Information Center: https://rarediseases.info.nih.gov/diseases/7893/disease [last accessed June 21, 2020].

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