Download PDF
Semin Liver Dis 2017; 37(02): 175-188
DOI: 10.1055/s-0037-1602764
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Disorders in Hepatic Copper Secretion: Wilson's Disease and Pleomorphic Syndromes

Vasiliki Lalioti
1   Department of Cell Biology and Immunology, Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Madrid, Spain
,
Akihito Tsubota
2   Division of Gastroenterology and Hepatology, Institute of Clinical Medicine and Research (ICMR), Jikei University School of Medicine, Kashiwa, Chiba, Japan
,
Ignacio V. Sandoval
1   Department of Cell Biology and Immunology, Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Madrid, Spain
› Author Affiliations
Further Information

Publication History

Publication Date:
31 May 2017 (online)

    Permissions and Reprints

Abstract

Wilson's disease (WD) is a rare disease the prevalence of which is higher than previously thought. Caused by genetic variations that target the copper (Cu) transporting P-ATPase Atp7b and disrupt the elimination of Cu by the liver, Atp7b truncations are associated with early severe liver disease and missense mutations with the late presentation of neurologic disorders. The asymptomatic initiation and false unimportance of initial symptoms often delays the crucial early diagnosis and a treatment that is lifesaving. The occasional acute liver failure persistently threatens the life of patients with WD. The gravity and progression of the disease are strongly dependent on the genetic background that organizes the response to the oxidative damage produced by the raised levels of free Cu. In this review, the authors focus on the prevalence, genetics, pathogenesis, clinical presentation, and treatment options in WD. They also discuss the new association of cuprotoxicosis with pleomorphic syndromes, of which MEDNIK is the first example, produced by genetic variations that disrupt the universal mechanisms of protein transport and thus perturb the traffic of Atp7b linked to Cu excretion.

Keywords

liver - copper - Atp7b - toxicosis
 

  • References

  • 1 McCord JM, Day Jr ED. Superoxide-dependent production of hydroxyl radical catalyzed by iron-EDTA complex. FEBS Lett 1978; 86 (01) 139-142
    CrossrefPubMedGoogle Scholar
  • 2 Predki PF, Sarkar B. Metal replacement in “zinc finger” and its effect on DNA binding. Environ Health Perspect 1994; 102 (Suppl. 03) 195-198
    CrossrefPubMedGoogle Scholar
  • 3 Compston A. Progressive lenticular degeneration: a familial nervous disease associated with cirrhosis of the liver, by S. A. Kinnier Wilson, (From the National Hospital, and the Laboratory of the National Hospital, Queen Square, London) Brain 1912: 34; 295-509. Brain 2009; 132 (Pt 8): 1997-2001
    CrossrefPubMedGoogle Scholar
  • 4 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 (04) 344-350
    CrossrefPubMedGoogle Scholar
  • 5 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 (04) 327-337
    CrossrefPubMedGoogle Scholar
  • 6 Coffey AJ, Durkie M, Hague S. , et al. A genetic study of Wilson's disease in the United Kingdom. Brain 2013; 136 (Pt 5): 1476-1487
    CrossrefPubMedGoogle Scholar
  • 7 Ohura T, Abukawa D, Shiraishi H. , et al. Pilot study of screening for Wilson disease using dried blood spots obtained from children seen at outpatient clinics. J Inherit Metab Dis 1999; 22 (01) 74-80
    CrossrefPubMedGoogle Scholar
  • 8 Hahn SH, Lee SY, Jang YJ. , et al. Pilot study of mass screening for Wilson's disease in Korea. Mol Genet Metab 2002; 76 (02) 133-136
    CrossrefPubMedGoogle Scholar
  • 9 Saito T. An assessment of efficiency in potential screening for Wilson's disease. J Epidemiol Community Health 1981; 35 (04) 274-280
    CrossrefPubMedGoogle Scholar
  • 10 Scheinberg IH. Penicillamine in Wilson's disease. Lancet 1982; 1 (8287): 1469
    PubMedGoogle Scholar
  • 11 Thomas GR, Bull PC, Roberts EA, Walshe JM, Cox DW. Haplotype studies in Wilson disease. Am J Hum Genet 1994; 54 (01) 71-78
    PubMedGoogle Scholar
  • 12 Petrukhin K, Fischer SG, Pirastu M. , et al. Mapping, cloning and genetic characterization of the region containing the Wilson disease gene. Nat Genet 1993; 5 (04) 338-343
    CrossrefPubMedGoogle Scholar
  • 13 Thomas GR, Roberts EA, Walshe JM, Cox DW. Haplotypes and mutations in Wilson disease. Am J Hum Genet 1995; 56 (06) 1315-1319
    PubMedGoogle Scholar
  • 14 Thomas GR, Jensson O, Gudmundsson G, Thorsteinsson L, Cox DW. Wilson disease in Iceland: a clinical and genetic study. Am J Hum Genet 1995; 56 (05) 1140-1146
    PubMedGoogle Scholar
  • 15 Thomas GR, Forbes JR, Roberts EA, Walshe JM, Cox DW. The Wilson disease gene: spectrum of mutations and their consequences. Nat Genet 1995; 9 (02) 210-217
    CrossrefPubMedGoogle Scholar
  • 16 Ferenci P. Regional distribution of mutations of the ATP7B gene in patients with Wilson disease: impact on genetic testing. Hum Genet 2006; 120 (02) 151-159
    CrossrefPubMedGoogle Scholar
  • 17 Firneisz G, Lakatos PL, Szalay F, Polli C, Glant TT, Ferenci P. Common mutations of ATP7B in Wilson disease patients from Hungary. Am J Med Genet 2002; 108 (01) 23-28
    CrossrefPubMedGoogle Scholar
  • 18 Caca K, Ferenci P, Kühn HJ. , et al. High prevalence of the H1069Q mutation in East German patients with Wilson disease: rapid detection of mutations by limited sequencing and phenotype-genotype analysis. J Hepatol 2001; 35 (05) 575-581
    CrossrefPubMedGoogle Scholar
  • 19 Nanji MS, Nguyen VT, Kawasoe JH. , et al. Haplotype and mutation analysis in Japanese patients with Wilson disease. Am J Hum Genet 1997; 60 (06) 1423-1429
    CrossrefPubMedGoogle Scholar
  • 20 Loudianos G, Dessì V, Lovicu M. , et al. Haplotype and mutation analysis in Greek patients with Wilson disease. Eur J Hum Genet 1998; 6 (05) 487-491
    CrossrefPubMedGoogle Scholar
  • 21 Margarit E, Bach V, Gómez D. , et al. Mutation analysis of Wilson disease in the Spanish population -- identification of a prevalent substitution and eight novel mutations in the ATP7B gene. Clin Genet 2005; 68 (01) 61-68
    CrossrefPubMedGoogle Scholar
  • 22 Loudianos G, Dessi V, Lovicu M. , et al. Molecular characterization of Wilson disease in the Sardinian population--evidence of a founder effect. Hum Mutat 1999; 14 (04) 294-303
    CrossrefPubMedGoogle Scholar
  • 23 Gomes A, Dedoussis GV. Geographic distribution of ATP7B mutations in Wilson disease. Ann Hum Biol 2016; 43 (01) 1-8
    CrossrefPubMedGoogle Scholar
  • 24 Gupta A, Aikath D, Neogi R. , et al. Molecular pathogenesis of Wilson disease: haplotype analysis, detection of prevalent mutations and genotype-phenotype correlation in Indian patients. Hum Genet 2005; 118 (01) 49-57
    CrossrefPubMedGoogle Scholar
  • 25 Santhosh S, Shaji RV, Eapen CE. , et al. Genotype phenotype correlation in Wilson's disease within families--a report on four south Indian families. World J Gastroenterol 2008; 14 (29) 4672-4676
    CrossrefPubMedGoogle Scholar
  • 26 Al Jumah M, Majumdar R, Al Rajeh S. , et al. A clinical and genetic study of 56 Saudi Wilson disease patients: identification of Saudi-specific mutations. Eur J Neurol 2004; 11 (02) 121-124
    CrossrefPubMedGoogle Scholar
  • 27 Todorov T, Balakrishnan P, Savov A, Socha P, Schmidt HH. Intragenic deletions in ATP7B as an unusual molecular genetics mechanism of Wilson's disease pathogenesis. PLoS One 2016; 11 (12) e0168372
    CrossrefPubMedGoogle Scholar
  • 28 Lee BH, Kim JH, Lee SY. , et al. Distinct clinical courses according to presenting phenotypes and their correlations to ATP7B mutations in a large Wilson's disease cohort. Liver Int 2011; 31 (06) 831-839
    CrossrefPubMedGoogle Scholar
  • 29 Okada T, Shiono Y, Hayashi H. , et al. Mutational analysis of ATP7B and genotype-phenotype correlation in Japanese with Wilson's disease. Hum Mutat 2000; 15 (05) 454-462
    CrossrefPubMedGoogle Scholar
  • 30 Chabik G, Litwin T, Członkowska A. Concordance rates of Wilson's disease phenotype among siblings. J Inherit Metab Dis 2014; 37 (01) 131-135
    CrossrefPubMedGoogle Scholar
  • 31 Usta J, Wehbeh A, Rida K. , et al. Phenotype-genotype correlation in Wilson disease in a large Lebanese family: association of c.2299insC with hepatic and of p. Ala1003Thr with neurologic phenotype. PLoS One 2014; 9 (11) e109727
    CrossrefPubMedGoogle Scholar
  • 32 Velez-Pardo C, Rio MJ, Moreno S, Ramírez-Gomez L, Correa G, Lopera F. New mutation (T1232P) of the ATP-7B gene associated with neurologic and neuropsychiatric dominance onset of Wilson's disease in three unrelated Colombian kindred. Neurosci Lett 2004; 367 (03) 360-364
    CrossrefPubMedGoogle Scholar
  • 33 Stapelbroek JM, Bollen CW, van Amstel JK. , et al. The H1069Q mutation in ATP7B is associated with late and neurologic presentation in Wilson disease: results of a meta-analysis. J Hepatol 2004; 41 (05) 758-763
    CrossrefPubMedGoogle Scholar
  • 34 Wilson DC, Phillips MJ, Cox DW, Roberts EA. Severe hepatic Wilson's disease in preschool-aged children. J Pediatr 2000; 137 (05) 719-722
    CrossrefPubMedGoogle Scholar
  • 35 Houwen RH, Roberts EA, Thomas GR, Cox DW. DNA markers for the diagnosis of Wilson disease. J Hepatol 1993; 17 (03) 269-276
    CrossrefPubMedGoogle Scholar
  • 36 Wu ZY, Wang N, Lin MT, Fang L, Murong SX, Yu L. Mutation analysis and the correlation between genotype and phenotype of Arg778Leu mutation in chinese patients with Wilson disease. Arch Neurol 2001; 58 (06) 971-976
    CrossrefPubMedGoogle Scholar
  • 37 Panagiotakaki E, Tzetis M, Manolaki N. , et al. Genotype-phenotype correlations for a wide spectrum of mutations in the Wilson disease gene (ATP7B). Am J Med Genet A 2004; 131 (02) 168-173
    PubMedGoogle Scholar
  • 38 Duc HH, Hefter H, Stremmel W. , et al. His1069Gln and six novel Wilson disease mutations: analysis of relevance for early diagnosis and phenotype. Eur J Hum Genet 1998; 6 (06) 616-623
    CrossrefPubMedGoogle Scholar
  • 39 Houwen RH, Juyn J, Hoogenraad TU, Ploos van Amstel JK, Berger R. H714Q mutation in Wilson disease is associated with late, neurological presentation. J Med Genet 1995; 32 (06) 480-482
    CrossrefPubMedGoogle Scholar
  • 40 Miyata M, Smith JD. Apolipoprotein E allele-specific antioxidant activity and effects on cytotoxicity by oxidative insults and beta-amyloid peptides. Nat Genet 1996; 14 (01) 55-61
    CrossrefPubMedGoogle Scholar
  • 41 Welsh-Bohmer KA, Gearing M, Saunders AM, Roses AD, Mirra S. Apolipoprotein E genotypes in a neuropathological series from the consortium to establish a registry for Alzheimer's disease. Ann Neurol 1997; 42 (03) 319-325
    CrossrefPubMedGoogle Scholar
  • 42 Alberts MJ, Graffagnino C, McClenny C. , et al. ApoE genotype and survival from intracerebral haemorrhage. Lancet 1995; 346 (8974): 575
    CrossrefPubMedGoogle Scholar
  • 43 Schiefermeier M, Kollegger H, Madl C. , et al. The impact of apolipoprotein E genotypes on age at onset of symptoms and phenotypic expression in Wilson's disease. Brain 2000; 123 (Pt 3): 585-590
    CrossrefPubMedGoogle Scholar
  • 44 Gromadzka G, Rudnicka M, Chabik G, Przybyłkowski A, Członkowska A. Genetic variability in the methylenetetrahydrofolate reductase gene (MTHFR) affects clinical expression of Wilson's disease. J Hepatol 2011; 55 (04) 913-919
    CrossrefPubMedGoogle Scholar
  • 45 Hamilton JP, Koganti L, Muchenditsi A. , et al. Activation of liver X receptor/retinoid X receptor pathway ameliorates liver disease in Atp7B(-/-) (Wilson disease) mice. Hepatology 2016; 63 (06) 1828-1841
    CrossrefPubMedGoogle Scholar
  • 46 Haywood S, Boursnell M, Loughran MJ. , et al. Copper toxicosis in non-COMMD1 Bedlington terriers is associated with metal transport gene ABCA12. J Trace Elem Med Biol 2016; 35: 83-89
    CrossrefPubMedGoogle Scholar
  • 47 Fu Y, Mukhamedova N, Ip S. , et al. ABCA12 regulates ABCA1-dependent cholesterol efflux from macrophages and the development of atherosclerosis. Cell Metab 2013; 18 (02) 225-238
    CrossrefPubMedGoogle Scholar
  • 48 Klomp AE, van de Sluis B, Klomp LW, Wijmenga C. The ubiquitously expressed MURR1 protein is absent in canine copper toxicosis. J Hepatol 2003; 39 (05) 703-709
    CrossrefPubMedGoogle Scholar
  • 49 Phillips-Krawczak CA, Singla A, Starokadomskyy P. , et al. COMMD1 is linked to the WASH complex and regulates endosomal trafficking of the copper transporter ATP7A. Mol Biol Cell 2015; 26 (01) 91-103
    CrossrefPubMedGoogle Scholar
  • 50 de Bie P, van de Sluis B, Burstein E. , et al. Distinct Wilson's disease mutations in ATP7B are associated with enhanced binding to COMMD1 and reduced stability of ATP7B. Gastroenterology 2007; 133 (04) 1316-1326
    CrossrefPubMedGoogle Scholar
  • 51 Roberts EA, Schilsky ML. ; American Association for Study of Liver Diseases (AASLD). Diagnosis and treatment of Wilson disease: an update. Hepatology 2008; 47 (06) 2089-2111
    CrossrefPubMedGoogle Scholar
  • 52 Weiss KH, Runz H, Noe B. , et al. Genetic analysis of BIRC4/XIAP as a putative modifier gene of Wilson disease. J Inherit Metab Dis 2010; 33 (Suppl. 03) S233-S240
    CrossrefPubMedGoogle Scholar
  • 53 European Association for Study of Liver. EASL clinical practice guidelines: Wilson's disease. J Hepatol 2012; 56 (03) 671-685
    CrossrefPubMed
  • 54 Ferenci P, Caca K, Loudianos G. , et al. Diagnosis and phenotypic classification of Wilson disease. Liver Int 2003; 23 (03) 139-142
    CrossrefPubMedGoogle Scholar
  • 55 Hurley LS, Keen CL, Lönnerdal B. Copper in fetal and neonatal development. Ciba Found Symp 1980; 79: 227-245
    PubMedGoogle Scholar
  • 56 Bingle CD, Epstein O, Srai SK, Gitlin JD. Hepatic caeruloplasmin-gene expression during development in the guinea-pig. Correlation with changes in hepatic copper metabolism. Biochem J 1991; 276 (Pt 3): 771-775
    CrossrefPubMedGoogle Scholar
  • 57 Czlonkowska A. A study of haemolysis in Wilson's disease. J Neurol Sci 1972; 16 (03) 303-314
    CrossrefPubMedGoogle Scholar
  • 58 Gow PJ, Smallwood RA, Angus PW, Smith AL, Wall AJ, Sewell RB. Diagnosis of Wilson's disease: an experience over three decades. Gut 2000; 46 (03) 415-419
    CrossrefPubMedGoogle Scholar
  • 59 Steindl P, Ferenci P, Dienes HP. , et al. Wilson's disease in patients presenting with liver disease: a diagnostic challenge. Gastroenterology 1997; 113 (01) 212-218
    CrossrefPubMedGoogle Scholar
  • 60 Sánchez-Albisua I, Garde T, Hierro L. , et al. A high index of suspicion: the key to an early diagnosis of Wilson's disease in childhood. J Pediatr Gastroenterol Nutr 1999; 28 (02) 186-190
    CrossrefPubMedGoogle Scholar
  • 61 Giacchino R, Marazzi MG, Barabino A. , et al. Syndromic variability of Wilson's disease in children. Clinical study of 44 cases. Ital J Gastroenterol Hepatol 1997; 29 (02) 155-161
    PubMedGoogle Scholar
  • 62 Frommer D, Morris J, Sherlock S, Abrams J, Newman S. Kayser-Fleischer-like rings in patients without Wilson's disease. Gastroenterology 1977; 72 (06) 1331-1335
    PubMedGoogle Scholar
  • 63 Polson RJ, Rolles K, Calne RY, Williams R, Marsden D. Reversal of severe neurological manifestations of Wilson's disease following orthotopic liver transplantation. Q J Med 1987; 64 (244) 685-691
    PubMedGoogle Scholar
  • 64 van Wassenaer-van Hall HN, van den Heuvel AG, Algra A, Hoogenraad TU, Mali WP. Wilson disease: findings at MR imaging and CT of the brain with clinical correlation. Radiology 1996; 198 (02) 531-536
    CrossrefPubMedGoogle Scholar
  • 65 Hitoshi S, Iwata M, Yoshikawa K. Mid-brain pathology of Wilson's disease: MRI analysis of three cases. J Neurol Neurosurg Psychiatry 1991; 54 (07) 624-626
    CrossrefPubMedGoogle Scholar
  • 66 Parekh JR, Agrawal PR. Wilson's disease: ‘face of giant panda’ and ‘trident’ signs together. Oxf Med Case Rep 2014; 20 (14) 16-17
    PubMedGoogle Scholar
  • 67 Walshe JM. The liver in Wilson's disease. In: Schiff L. , Schiffer, eds. Diseases of the Liver. 6th ed. Philadelphia: Lippincott; 1987: 1037-1050
    Google Scholar
  • 68 Okada T, Shiono Y, Kaneko Y. , et al. High prevalence of fulminant hepatic failure among patients with mutant alleles for truncation of ATP7B in Wilson's disease. Scand J Gastroenterol 2010; 45 (10) 1232-1237
    CrossrefPubMedGoogle Scholar
  • 69 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
  • 70 Reuben A, Tillman H, Fontana RJ. , et al. Outcomes in adults with acute liver failure between 1998 and 2013: an observational cohort study. Ann Intern Med 2016; 164 (11) 724-732
    CrossrefPubMedGoogle Scholar
  • 71 Walshe JM, Dixon AK. Dangers of non-compliance in Wilson's disease. Lancet 1986; 1 (8485): 845-847
    PubMedGoogle Scholar
  • 72 Eisenbach C, Sieg O, Stremmel W, Encke J, Merle U. Diagnostic criteria for acute liver failure due to Wilson disease. World J Gastroenterol 2007; 13 (11) 1711-1714
    CrossrefPubMedGoogle Scholar
  • 73 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
  • 74 Weiss KH, Gotthardt DN, Klemm D. , et al. Zinc monotherapy is not as effective as chelating agents in treatment of Wilson disease. Gastroenterology 2011; 140 (04) 1189-1198.e1
    CrossrefPubMedGoogle Scholar
  • 75 Walshe JM. Wilson's disease; new oral therapy. Lancet 1956; 270 (6906): 25-26
    PubMedGoogle Scholar
  • 76 Walshe JM. Treatment of Wilson's disease with trientine (triethylene tetramine) dihydrochloride. Lancet 1982; 1 (8273): 643-647
    PubMedGoogle Scholar
  • 77 Weiss KH, Thurik F, Gotthardt DN. , et al; EUROWILSON Consortium Efficacy and safety of oral chelators in treatment of patients with Wilson disease. Clin Gastroenterol Hepatol 2013; 11 (08) 1028-35.e1 , 2
    CrossrefPubMedGoogle Scholar
  • 78 Iorio R, D'Ambrosi M, Marcellini M. , et al; Hepatology Committee of Italian Society of Paediatric Gastroenterology Hepatology and Nutrition. Serum transaminases in children with Wilson's disease. J Pediatr Gastroenterol Nutr 2004; 39 (04) 331-336
    CrossrefPubMedGoogle Scholar
  • 79 Weiss KH, Stremmel W. Evolving perspectives in Wilson disease: diagnosis, treatment and monitoring. Curr Gastroenterol Rep 2012; 14 (01) 1-7
    CrossrefPubMedGoogle Scholar
  • 80 Stuerenburg HJ. CSF copper concentrations, blood-brain barrier function, and coeruloplasmin synthesis during the treatment of Wilson's disease. J Neural Transm (Vienna) 2000; 107 (03) 321-329
    CrossrefPubMedGoogle Scholar
  • 81 Brewer GJ, Askari F, Lorincz MT. , 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 2006; 63 (04) 521-527
    CrossrefPubMedGoogle Scholar
  • 82 Oestreicher P, Cousins RJ. Copper and zinc absorption in the rat: mechanism of mutual antagonism. J Nutr 1985; 115 (02) 159-166
    CrossrefPubMedGoogle Scholar
  • 83 Ferenci P. Wilson disease. Indian J Gastroenterol 2001; 20 (Suppl. 01) C71-C78
    PubMedGoogle Scholar
  • 84 Chen JC, Chuang CH, Wang JD, Wang CW. combination therapy using chelating agent and zinc for Wilson's disease. J Med Biol Eng 2015; 35 (06) 697-708
    CrossrefPubMedGoogle Scholar
  • 85 Brewer GJ, Hedera P, Kluin KJ. , et al. 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 2003; 60 (03) 379-385
    CrossrefPubMedGoogle Scholar
  • 86 Brewer GJ. Zinc and tetrathiomolybdate for the treatment of Wilson's disease and the potential efficacy of anticopper therapy in a wide variety of diseases. Metallomics 2009; 1 (03) 199-206
    CrossrefPubMedGoogle Scholar
  • 87 Brewer GJ, Dick RD, Yuzbasiyan-Gurkin V, Tankanow R, Young AB, Kluin KJ. Initial therapy of patients with Wilson's disease with tetrathiomolybdate. Arch Neurol 1991; 48 (01) 42-47
    CrossrefPubMedGoogle Scholar
  • 88 Wapnir RA. Copper absorption and bioavailability. Am J Clin Nutr 1998; 67 (5, Suppl) 1054S-1060S
    CrossrefPubMedGoogle Scholar
  • 89 Durand F, Bernuau J, Giostra E. , et al. Wilson's disease with severe hepatic insufficiency: beneficial effects of early administration of D-penicillamine. Gut 2001; 48 (06) 849-852
    CrossrefPubMedGoogle Scholar
  • 90 Harada M. Management for acute liver failure of Wilson disease: indication for liver transplantation. Hepatol Res 2016
    PubMedGoogle Scholar
  • 91 Dhawan A, Taylor RM, Cheeseman P, De Silva P, Katsiyiannakis L, Mieli-Vergani G. Wilson's disease in children: 37-year experience and revised King's score for liver transplantation. Liver Transpl 2005; 11 (04) 441-448
    CrossrefPubMedGoogle Scholar
  • 92 Nazer H, Ede RJ, Mowat AP, Williams R. Wilson's disease: clinical presentation and use of prognostic index. Gut 1986; 27 (11) 1377-1381
    CrossrefPubMedGoogle Scholar
  • 93 Petrasek J, Jirsa M, Sperl J. , et al. Revised King's College score for liver transplantation in adult patients with Wilson's disease. Liver Transpl 2007; 13 (01) 55-61
    CrossrefPubMedGoogle Scholar
  • 94 Schilsky ML. Liver transplantation for Wilson's disease. Ann N Y Acad Sci 2014; 1315: 45-49
    CrossrefPubMedGoogle Scholar
  • 95 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
  • 96 Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 2012; 337 (6096): 816-821
    CrossrefPubMedGoogle Scholar
  • 97 Gasiunas G, Barrangou R, Horvath P, Siksnys V. Cas9-crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria. Proc Natl Acad Sci U S A 2012; 109 (39) E2579-E2586
    CrossrefPubMedGoogle Scholar
  • 98 Patel M. Targeting oxidative stress in central nervous system disorders. Trends Pharmacol Sci 2016; 37 (09) 768-778
    CrossrefPubMedGoogle Scholar
  • 99 Tsubota A, Yoshikawa T, Nariai K. , et al. Bovine lactoferrin potently inhibits liver mitochondrial 8-OHdG levels and retrieves hepatic OGG1 activities in Long-Evans Cinnamon rats. J Hepatol 2008; 48 (03) 486-493
    CrossrefPubMedGoogle Scholar
  • 100 Schaefer M, Hopkins RG, Failla ML, Gitlin JD. Hepatocyte-specific localization and copper-dependent trafficking of the Wilson's disease protein in the liver. Am J Physiol 1999; 276 (3 Pt 1): G639-G646
    PubMedGoogle Scholar
  • 101 Dmitriev OY, Bhattacharjee A, Nokhrin S, Uhlemann EM, Lutsenko S. Difference in stability of the N-domain underlies distinct intracellular properties of the E1064A and H1069Q mutants of copper-transporting ATPase ATP7B. J Biol Chem 2011; 286 (18) 16355-16362
    CrossrefPubMedGoogle Scholar
  • 102 Gupta A, Bhattacharjee A, Dmitriev OY. , et al. Cellular copper levels determine the phenotype of the Arg875 variant of ATP7B/Wilson disease protein. Proc Natl Acad Sci U S A 2011; 108 (13) 5390-5395
    CrossrefPubMedGoogle Scholar
  • 103 Braiterman L, Nyasae L, Leves F, Hubbard AL. Critical roles for the COOH terminus of the Cu-ATPase ATP7B in protein stability, trans-Golgi network retention, copper sensing, and retrograde trafficking. Am J Physiol Gastrointest Liver Physiol 2011; 301 (01) G69-G81
    CrossrefPubMedGoogle Scholar
  • 104 Lalioti V, Hernandez-Tiedra S, Sandoval IV. DKWSLLL, a versatile DXXXLL-type signal with distinct roles in the Cu(+)-regulated trafficking of ATP7B. Traffic 2014; 15 (08) 839-860
    CrossrefPubMedGoogle Scholar
  • 105 Beare JM, Nevin NC, Froggatt P, Kernohan DC, Allen IV. Atypical erythrokeratoderma with deafness, physical retardation and peripheral neuropathy. Br J Dermatol 1972; 87 (04) 308-314
    CrossrefPubMedGoogle Scholar
  • 106 Saba TG, Montpetit A, Verner A. , et al. An atypical form of erythrokeratodermia variabilis maps to chromosome 7q22. Hum Genet 2005; 116 (03) 167-171
    CrossrefPubMedGoogle Scholar
  • 107 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): 872-881
    CrossrefPubMedGoogle Scholar
  • 108 Montpetit A, Côté S, Brustein E. , et al. Disruption of AP1S1, causing a novel neurocutaneous syndrome, perturbs development of the skin and spinal cord. PLoS Genet 2008; 4 (12) e1000296
    CrossrefPubMedGoogle Scholar
  • 109 Bonnemaison ML, Bäck N, Duffy ME, Ralle M, Mains RE, Eipper BA. Adaptor protein-1 complex affects the endocytic trafficking and function of peptidylglycine α-amidating monooxygenase, a luminal cuproenzyme. J Biol Chem 2015; 290 (35) 21264-21279
    CrossrefPubMedGoogle Scholar
  • 110 Hodgkinson VL, Dale JM, Garcia ML. , et al. X-linked spinal muscular atrophy in mice caused by autonomous loss of ATP7A in the motor neuron. J Pathol 2015; 236 (02) 241-250
    CrossrefPubMedGoogle Scholar
  • 111 Kennerson ML, Nicholson GA, Kaler SG. , et al. Missense mutations in the copper transporter gene ATP7A cause X-linked distal hereditary motor neuropathy. Am J Hum Genet 2010; 86 (03) 343-352
    CrossrefPubMedGoogle Scholar
  • 112 Lalioti V, Peiró R, Pérez-Berlanga M. , et al. Basolateral sorting and transcytosis define the Cu+-regulated translocation of ATP7B to the bile canaliculus. J Cell Sci 2016; 129 (11) 2190-2201
    CrossrefPubMedGoogle Scholar
  • 113 Nyasae LK, Schell MJ, Hubbard AL. Copper directs ATP7B to the apical domain of hepatic cells via basolateral endosomes. Traffic 2014; 15 (12) 1344-1365
    CrossrefPubMedGoogle Scholar
  • 114 Stuehler B, Reichert J, Stremmel W, Schaefer M. Analysis of the human homologue of the canine copper toxicosis gene MURR1 in Wilson disease patients. J Mol Med (Berl) 2004; 82 (09) 629-634
    PubMedGoogle Scholar
  • 115 Vonk WI, Bartuzi P, de Bie P. , et al. Liver-specific Commd1 knockout mice are susceptible to hepatic copper accumulation. PLoS One 2011; 6 (12) e29183
    CrossrefPubMedGoogle Scholar
  • 116 Donoso M, Cancino J, Lee J. , et al. Polarized traffic of LRP1 involves AP1B and SNX17 operating on Y-dependent sorting motifs in different pathways. Mol Biol Cell 2009; 20 (01) 481-497
    CrossrefPubMedGoogle Scholar
  • 117 Braiterman L, Nyasae L, Guo Y, Bustos R, Lutsenko S, Hubbard A. Apical targeting and Golgi retention signals reside within a 9-amino acid sequence in the copper-ATPase, ATP7B. Am J Physiol Gastrointest Liver Physiol 2009; 296 (02) G433-G444
    CrossrefPubMedGoogle Scholar
  • 118 Roelofsen H, Wolters H, Van Luyn MJ, Miura N, Kuipers F, Vonk RJ. Copper-induced apical trafficking of ATP7B in polarized hepatoma cells provides a mechanism for biliary copper excretion. Gastroenterology 2000; 119 (03) 782-793
    CrossrefPubMedGoogle Scholar
  • 119 Schaefer M, Roelofsen H, Wolters H. , et al. Localization of the Wilson's disease protein in human liver. Gastroenterology 1999; 117 (06) 1380-1385
    CrossrefPubMedGoogle Scholar
  • 120 Hernandez S, Tsuchiya Y, García-Ruiz JP. , et al. ATP7B copper-regulated traffic and association with the tight junctions: copper excretion into the bile. Gastroenterology 2008; 134 (04) 1215-1223
    CrossrefPubMedGoogle Scholar
  • 121 Polishchuk EV, Concilli M, Iacobacci S. , et al. Wilson disease protein ATP7B utilizes lysosomal exocytosis to maintain copper homeostasis. Dev Cell 2014; 29 (06) 686-700
    CrossrefPubMedGoogle Scholar
  • 122 Zatulovskaia YA, Ilyechova EY, Puchkova LV. The features of copper metabolism in the rat liver during development. PLoS One 2015; 10 (10) e0140797
    CrossrefPubMedGoogle Scholar
  • 123 McMillan KJ, Gallon M, Jellett AP. , et al. Atypical parkinsonism-associated retromer mutant alters endosomal sorting of specific cargo proteins. J Cell Biol 2016; 214 (04) 389-399
    CrossrefPubMedGoogle Scholar
  • 124 Vilariño-Güell C, Wider C, Ross OA. , et al. VPS35 mutations in Parkinson disease. Am J Hum Genet 2011; 89 (01) 162-167
    CrossrefPubMedGoogle Scholar
  • 125 Zimprich A, Benet-Pagès A, Struhal W. , et al. A mutation in VPS35, encoding a subunit of the retromer complex, causes late-onset Parkinson disease. Am J Hum Genet 2011; 89 (01) 168-175
    CrossrefPubMedGoogle Scholar
  • 126 Sechi G, Antonio Cocco G, Errigo A. , et al. Three sisters with very-late-onset major depression and parkinsonism. Parkinsonism Relat Disord 2007; 13 (02) 122-125
    CrossrefPubMedGoogle Scholar
  • 127 Johnson S. Is Parkinson's disease the heterozygote form of Wilson's disease: PD = 1/2 WD?. Med Hypotheses 2001; 56 (02) 171-173
    CrossrefPubMedGoogle Scholar
  • 128 Lichtmannegger J, Leitzinger C, Wimmer R. , et al. Methanobactin reverses acute liver failure in a rat model of Wilson disease. J Clin Invest 2016; 126 (07) 2721-2735
    CrossrefPubMedGoogle Scholar
  • 129 Tsivkovskii R, Efremov RG, Lutsenko S. The role of the invariant His-1069 in folding and function of the Wilson's disease protein, the human copper-transporting ATPase ATP7B. J Biol Chem 2003; 278 (15) 13302-13308
    CrossrefPubMedGoogle Scholar