Advance in the pathogenesis and treatment of Wilson disease

Translational Neurodegeneration

Zhi-Ying Wu¹  Qin-Yun Dong¹ 

[1] Department of Neurology and Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, 12 Wulumuqi Zhong Road, Shanghai, 200040, China

关键词: Liver transplantation;    Ammonium tetrathiomolybdate;    Zinc;    Trientine;    D-penicillamin;    COMMD1;    ATP7B;    Copper;    Wilson disease;   

Others  :  838860
DOI  :  10.1186/2047-9158-1-23

 received in 2012-09-26, accepted in 2012-11-21,  发布年份 2012

【 摘 要 】

Wilson disease is an autosomal recessive disorder of copper metabolism. Diagnosis depends primarily on clinical features, biochemical parameters and the presence of the Kayser-Fleischer ring. Genetic analysis for mutations within ATP7B is a convincing diagnostic tool. The traditional treatment for WD includes chelation of excessive copper accumulation and reduction of copper intake. Medical therapy is effective but WD is not yet curable. Liver transplantation is especially helpful for patients who fail to respond to medical therapy or present with fulminant liver failure, although evaluation of its long-term effect are still in need.

【 授权许可】

   
2012 Dong and Wu; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Huster D: Wilson disease. Best Pract Res Cl Ga 2010, 24(5):531-539.
• [2]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(3):139-142.
• [3]Gitlin N: Wilson's disease: the scourge of copper. J Hepatol 1998, 28(4):734-739.
• [4]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 ATPase. Nat Genet 1993, 3(1):7-13.
• [5]Valentine JS, Gralla EB: Biochemistry - delivering copper inside yeast and human cells. Science 1997, 278(5339):817-818.
• [6]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(4):327-337.
• [7]Tanzi RE, Petrukhin K, Chernov I, Pellequer JL, Wasco W, Ross B, Romano DM, Parano E, Pavone L, Brzustowicz LM, et al.: The Wilson disease gene is a copper transporting atpase with homology to the Menkes disease gene. Nat Genet 1993, 5(4):344-350.
• [8]Hsi G, Cullen LA, Macintyre G, Chen MM, Glerum DM, Cox DW: Sequence variation in the ATP-binding domain of the Wilson disease transporter, ATP7B, affects copper transport in a yeast model system. Hum Mutat 2008, 29(4):491-501.
• [9]Forbes JR, Cox DW: Copper-dependent trafficking of Wilson disease mutant ATP7B proteins. Hum Mol Genet 2000, 9(13):1927-1935.
• [10]Huster D, Kuhne A, Bhattacharjee A, Raines L, Jantsch V, Noe J, Schirrmeister W, Sommerer I, Sabri O, Berr F, et al.: Diverse functional properties of Wilson disease ATP7b variants. Gastroenterol 2012, 142(4):429-947.
• [11]van den Berghe P, Stapelbroek JM, Krieger E, de Bie P, van de Graaf S, de Groot R, van Beurden E, Houwen R, Berger R, Klomp L: Reduced expression of atp7b affected by wilson disease-causing mutations is rescued by pharmacological folding chaperones 4-phenylbutyrate and curcumin. Hepatol 2009, 50(6):1783-1795.
• [12]Zischka H, Lichtmannegger J, Schmitt S, Jagemann N, Schulz S, Wartini D, Jennen L, Rust C, Larochette N, Galluzzi L, et al.: Liver mitochondrial membrane crosslinking and destruction in a rat model of Wilson disease. J Clin Invest 2011, 121(4):1508-1518.
• [13]Sauer SW, Merle U, Opp S, Haas D, Hoffmann GF, Stremmel W, Okun JG: Severe dysfunction of respiratory chain and cholesterol metabolism in Atp7b(−/−) mice as a model for Wilson disease. Bba-Mol Basis Dis 2011, 1812(12):1607-1615.
• [14]Koopman W, Nijtmans L, Dieteren C, Roestenberg P, Valsecchi F, Smeitink J, Willems P: Mammalian mitochondrial complex i: biogenesis, regulation, and reactive oxygen species generation. Antioxid Redox Signal 2010, 12(12):1431-1470.
• [15]Yurkova IL, Arnhold J, Fitzl G, Huster D: Fragmentation of mitochondrial cardiolipin by copper ions in the Atp7b(−/−) mouse model of Wilson's disease. Chem Phys Lipids 2011, 164(5):393-400.
• [16]Strand S, Hofmann WJ, Grambihler A, Hug H, Volkmann M, Otto G, Wesch H, Mariani SM, Hack V, Stremmel W, et al.: Hepatic failure and liver cell damage in acute Wilson's disease involve CD95 (APO-1/Fas) mediated apoptosis. Nat Med 1998, 4(5):588-593.
• [17]Wolfe JT, Ross D, Cohen GM: A role for metals and free-radicals in the induction of apoptosis in thymocytes. FEBS Lett 1994, 352(1):58-62.
• [18]Paris I, Perez-Pastene C, Couve E, Caviedes P, LeDoux S, Segura-Aguilar J: Copper center dot dopamine complex induces mitochondrial autophagy preceding caspase-independent apoptotic cell death. J Biol Chem 2009, 284(20):13306-13315.
• [19]van de Sluis B, Rothuizen J, Pearson PL, van Oost BA, Wijmenga C: Identification of a new copper metabolism gene by positional cloning in a purebred dog population. Hum Mol Genet 2002, 11(2):165-173.
• [20]de Bie P, van de Sluis B, Burstein E, van den Berghe PVE, Muller P, Berger R, Gitlin JD, Wijmenga C, Klomp LWJ: Distinct Wilson's disease mutations in ATP7B are associated with enhanced binding to COMMD1 and reduced stability of ATP7B. Gastroenterol 2007, 133(4):1316-1326.
• [21]Materia S, Cater MA, Klomp L, Mercer J, La Fontaine S: Clusterin and COMMD1 independently regulate degradation of the mammalian copper ATPases Atp7A nd Atp7B. J Biol Chem 2012, 287(4):2485-2499.
• [22]Wu ZY, Zhao GX, Chen WJ, Wang N, Wan B, Lin MT, Murong SX, Yu L: Mutation analysis of 218 Chinese patients with Wilson disease revealed no correlation between the canine copper toxicosis gene MURR1 and Wilson disease. J Mol Med-Jmm 2006, 84(5):438-442.
• [23]Mufti AR, Burstein E, Csomos RA, Graf P, Wilkinson JC, Dick RD, Challa M, Son JK, Bratton SB, Su GL, et al.: XIAP is a copper binding protein dereaulated in Wilson's disease and other copper toxicosis disorders. Mol Cell 2006, 21(6):775-785.
• [24]Mufti AR, Burstein E, Duckett CS: XIAP: cell death regulation meets copper homeostasis. Arch Biochem Biophys 2007, 463(2):168-174.
• [25]Huppke P, Brendel C, Korenke GC, Marquardt I, Donsante A, Yi L, Hicks JD, Steinbach PJ, Wilson C, Elpeleg O, et al.: Molecular and biochemical characterization of a unique mutation in CCS, the human copper chaperone to superoxide dismutase. Hum Mutat 2012, 33(8):1207-1215.
• [26]Wu ZY, Lin MT, Murong SX, Wang N: Molecular diagnosis and prophylactic therapy for presymptomatic Chinese patients with Wilson disease. Arch Neurol-Chicago 2003, 60(5):737-741.
• [27]Ferenci P, Czlonkowska A, Stremmel W, Houwen R, Rosenberg W, Schilsky M, Jansen P, Moradpour D, Gitlin J: EASL clinical practice guidelines: Wilson's disease. J Hepatol 2012, 56(3):671-685.
• [28]Brewer GJ: Novel therapeutic approaches to the treatment of Wilson's disease. Expert Opin Pharmocother 2006, 7(3):317-324.
• [29]Brewer GJ, Askari F, Dick RB, Sitterly J, Fink JK, Carlson M, Kluin KJ, Lorincz MT: Treatment of Wilson's disease with tetrathiomolybdate: V. control of free copper by tetrathiomolybdate and a comparison with trientine. Transl Res 2009, 154(2):70-77.
• [30]McArdle HJ, Kyriakou P, Grimes A, Mercer JF, Danks DM: The effect of D-penicillamine on metallothionein mRNA levels and copper distribution in mouse hepatocytes. Chem Biol Interact 1990, 75(3):315-324.
• [31]Balamurugan K, Schaffner W: Copper homeostasis in eukaryotes: teetering on a tightrope. Bba-Mol Cell Res 2006, 1763(7):737-746.
• [32]Xu H, Nakagawa A, Aoyama Y: Suppressive effects of dietary D-penicillamine on the gene expression of hepatic metallothionein-1 and protein level of hepatic metallothionein in Long-Evans Cinnamon rats. Nutr Res 2004, 24(11):935-944.
• [33]Gibbs K, Walshe JM: Penicillamine and pyridoxine requirements in man. Lancet 1966, 1(7430):175.
• [34]Brewer GJ: Penicillamine should not be used as initial therapy in Wilson's disease. Movement Disord 1999, 14(4):551-554.
• [35]Walshe JM: Penicillamine: the treatment of first choice for patients with Wilson's disease. Movement Disord 1999, 14(4):545-550.
• [36]Sternlieb I, Scheinberg IH: Prophylaxis of Wilson's disease. N Engl J Med 1968, 278(20):1125.
• [37]Bienaime F, Clerbaux G, Plaisier E, Mougenot B, Ronco P, Rougier J: D-penicillamine-induced ANCA-associated crescentic glomerulonephritis in Wilson disease. Am J Kidney Dis 2007, 50(5):821-825.
• [38]Becuwe C, Dalle S, Ronger-Savle S, Skowron F, Balme B, Kanitakis J, Thomas L: Elastosis perforans serpiginosa associated with pseudo-pseudoxanthoma elasticum during treatment of Wilson's disease with penicillamine. Dermatol 2005, 210(1):60-63.
• [39]Wiggelinkhuizen M, Tilanus M, Bollen CW, Houwen R: Systematic review: clinical efficacy of chelator agents and zinc in the initial treatment of Wilson disease. Aliment Pharm Therap 2009, 29(9):947-958.
• [40]Taylor RM, Chen Y, Dhawan A: Triethylene tetramine dihydrochloride (trientine) in children with Wilson disease: experience at King's College Hospital and review of the literature. Eur J Pediatr 2009, 168(9):1061-1068.
• [41]Benbir G, Gunduz A, Ertan S, Ozkara C: Partial status epilepticus induced by hypocupremia in a patient with Wilson's disease. Seizure-Eur J Epilep 2010, 19(9):602-604.
• [42]Chen DB, Feng L, Lin XP, Zhang W, Li FR, Liang XL, Li XH: Penicillamine increases free copper and enhances oxidative stress in the brain of toxic milk mice. PLoS One 2012., 7(5) e377095
• [43]Ping CC, Hassan Y, Aziz NA, Ghazali R, Awaisu A: Discontinuation of penicillamine in the absence of alternative orphan drugs (trientine-zinc): a case of decompensated liver cirrhosis in Wilson's disease. J Clin Pharm Ther 2007, 32(1):101-107.
• [44]Walshe JM: Treatment of wilsons-disease with trientine (triethylene tetramine) dihydrochloride. Lancet 1982, 1(8273):643-647.
• [45]Brewer GJ, Askari F, Lorincz MT, Carlson M, Schilsky M, Kluin KJ, Hedera P, Moretti P, Fink MK, Tankanow R, 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-Chicago 2006, 63(4):521-527.
• [46]Weiss KH, Schots M, Gotthardt DN, Ferenci-Foerster D, Maieron A, Stauber R, Reuner U, Houwen R, Stremmel W, Ferenci P: Efficacy and safety of D-penicillamine and trientine for the treatment of Wilson disease. J Hepatol 2011, 541:S1.
• [47]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. Gastroenterol 2011, 140(4):1189.
• [48]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(6):385-390.
• [49]Brewer GJ, Dick RD, Johnson VD, Brunberg JA, Kluin KJ, Fink JK: Treatment of Wilson's disease with zinc: XV - long-term follow-up studies. J Lab Clin Med 1998, 132(4):264-278.
• [50]Bruha R, Marecek Z, Pospisilova L, Nevsimalova S, Vitek L, Martasek P, Nevoral J, Petrtyl J, Urbanek P, Jiraskova A, et al.: Long-term follow-up of Wilson disease: natural history, treatment, mutations analysis and phenotypic correlation. Liver Int 2011, 31(1):83-91.
• [51]Mills CF, Elgallad TT, Bremner I: Effects of molybdate, sulfide, and tetrathiomolybdate on copper-metabolism in rats. J Inorg Biochem 1981, 14(3):189-207.
• [52]Mills CF, Elgallad TT, Bremner I, Wenham G: copper and molybdenum absorption by rats given ammonium tetrathiomolybdate. J Inorg Biochem 1981, 14(2):163-175.
• [53]Brewer GJ, Hedera P, Kluin KJ, Carlson M, Askari F, Dick RB, Sitterly J, Fink JK: 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-Chicago 2003, 60(3):379-385.
• [54]Lorincz MT: Neurologic Wilson's disease. In Annals of the New York Academy of Sciences. Volume 1184. Edited by Johnson RT. Malden, MA USA: Wiley-Blackwell; 2010:173-187.
• [55]Holscher S, Leinweber B, Hefter H, Reuner U, Gunther P, Weiss KH, Oertel WH, Moller JC: Evaluation of the symptomatic treatment of residual neurological symptoms in Wilson disease. Eur Neurol 2010, 64(2):83-87.
• [56]Micheli F, Tschopp L, Cersosimo MG: Oxcarbazepine-responsive paroxysmal kinesigenic dyskinesia in Wilson disease. Clin Neuropharmacol 2011, 34(6):262-264.
• [57]De Fabregues O, Palasi A, Callen A, Hernandez-Vara J, Alvarez-Sabin J: Successful treatment of Wilson's disease dystonia with botulinum toxin. Movement Disord 2010, 25S(7):S234.
• [58]Paliwal VK, Gupta PK, Pradhan S: Gabapentin as a rescue drug in D-penicillamine-induced status dystonicus in patients with Wilson disease. Neurol India 2010, 58(5):761-763.
• [59]Yang RM, Chen N: The outcomes and followup of intergrated therapy of traditional Chinese medicine and chelation agents in 198 patients. Chin J Integr Med 2002, 22(9):657-659. article in Chinese
• [60]Wang Y, Xie CL, Fu DL, Lu L, Lin Y, Dong QQ, Wang XT, Zheng GQ: Clinical efficacy and safety of Chinese herbal medicine for Wilson's disease: a systematic review of 9 randomized controlled trials. Complement Ther Med 2012, 20(3):143-154.
• [61]Sen S, Felldin M, Steiner C, Larsson B, Gillett GT, Olausson M, Williams R, Jalan R: Albumin dialysis and Molecular Adsorbents Recirculating System (MARS) for acute Wilson's disease. Liver Transpl 2002, 8(10):962-967.
• [62]Arnon R, Annunziato R, Schilsky M, Miloh T, Willis A, Sturdevant M, Sakworawich A, Suchy F, Kerkar N: Liver transplantation for children with Wilson disease: comparison of outcomes between children and adults. Clin Transplant 2011, 25(1):E52-E60.
• [63]Ozcay F, Bayrakci US, Baskin E, Sakalli H, Canan O, Karakayali H, Haberal M: Long term follow-up of glomerular and tubular functions in liver transplanted patients with Wilson's disease. Pediatr Transplant 2008, 12(7):785-789.
• [64]Narumi S, Umehara M, Toyoki Y, Ishido K, Kudo D, Kimura N, Kobayashi T, Sugai M, Hakamada K: Liver transplantation for wilson's disease in pediatric patients: decision making and timing. Transplant P 2012, 44(2):478-480.
• [65]Murray KF, Carithers RL: AASLD practice guidelines: evaluation of the patient for liver transplantation. Hepatol 2005, 41(6):1407-1432.
• [66]Hermann W, Eggers B, Wagner A: The indication for liver transplant to improve neurological symptoms in a patient with Wilson's disease. J Neurol 2002, 249(12):1733-1734.
• [67]Geissler I, Heinemann K, Rohm S, Hauss J, Lamesch P: Liver transplantation for hepatic and neurological Wilson's disease. Transplant P 2003, 35(4):1445-1446.
• [68]Suzuki S, Sato Y, Ichida T, Hatakeyama K: Recovery of severe neurologic manifestations of Wilson's disease after living-related liver transplantation: a case report. Transplant P 2003, 35(1):385-386.
• [69]Stracciari A, Tempestini A, Borghi A, Guarino M: Effect of liver transplantation on neurological manifestations in Wilson disease. Arch Neurol-Chicago 2000, 57(3):384-386.
• [70]Suess T, Bokemeyer M, Schomerus G, Donnerstag F, Manns MP, Klempnauer J, Kolbe H, Weissenborn K: Video documented follow-up of liver transplantation in Wilson's disease with predominant neurological manifestation. Movement Disord 2007, 22(7):1036-1038.
• [71]Schilsky ML, Scheinberg IH, Sternlieb I: Liver-transplantation for wilsons-disease - indications and outcome. Hepatology 1994, 19(3):583-587.
• [72]Erol I, Alehan F, Ozcay F, Canan O, Haberal M: Neurological complications of liver transplantation in pediatric patients: a single center experience. Pediatr Transplant 2007, 11(2):152-159.
• [73]Enrol I, Alehan F, Ozcay F, Canan O, Haberal M: Neurologic complications of liver transplantation in pediatric patients with the hepatic form of Wilson's disease. J Child Neurol 2008, 23(3):293-300.
• [74]Medici V, Mirante VG, Fassati LR, Pompili M, Forti D, Del Gaudio M, Trevisan CP, Cillo U, Sturniolo GC, Fagiuoli S: Liver transplantation for Wilson's disease: the burden of neurological and psychiatric disorders. Liver Transplant 2005, 11(9):1056-1063.
• [75]Carithers RL: Liver transplantation. Liver Transplant 2000, 6(1):122-135.
• [76]Walshe JM: The management of pregnancy in Wilsons-disease treated with trientine. Q J Med 1986, 58(225):81-87.
• [77]Brewer GJ, Johnson VD, Dick RD, Hedera P, Fink JK, Kluin KJ: Treatment of Wilson's disease with zinc. XVII: Treatment during pregnancy. Hepatol 2000, 31(2):364-370.
• [78]Messner U, Gunter HH, Niesert S: Wilson's disease and pregnancy. Z Geburtshilfe Neonatol 1998, 202(2):77-79.
• [79]Roberts EA, Schilsky ML: Diagnosis and treatment of Wilson disease: an update. Hepatol 2008, 47(6):2089-2111.
• [80]Malhi H, Joseph B, Schilsky ML, Gupta S: Development of cell therapy strategies to overcome copper toxicity in the LEC rat model of Wilson disease. Regen Med 2008, 3(2):165-173.