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Wilson’s Disease in China

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Abstract

Wilson’s disease (WD) is an autosomal recessive disorder of copper metabolism. Its incidence is higher in China than in western countries. ATP7B is the causative gene and encodes a P-type ATPase, which participates in the synthesis of holoceruloplasmin and copper excretion. Disease-causing variants of ATP7B disrupt the normal structure or function of the enzyme and cause copper deposition in multiple organs, leading to diverse clinical manifestations. Given the variety of presentations, misdiagnosis is not rare. Genetic diagnosis plays an important role and has gradually become a routine test in China. The first Chinese spectrum of disease-causing mutations of ATP7B has been established. As a remediable hereditary disorder, most WD patients have a good prognosis with an early diagnosis and chelation treatment. However, clinical trials are relatively few in China, and most treatments are based on the experience of experts and evidences from other countries. It is necessary to study and develop appropriate regimens specific for Chinese WD patients.

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References

  1. Cheng YL. Hepatolenticular degeneration (pseudosclerosis, progressive lenticular degeneration and torsion spasm) review of literature and report of two cases. Chin Med J 1932, 46: 347–364.

    Google Scholar 

  2. Hu WB, Han YZ, Xue BC, Cheng N, Sun DY, Ye DQ, et al. Epidemiological investigation of Wilson disease in Hanshan county, Anhui Province. Chin Med J 2010, 91: 894–897.

    Google Scholar 

  3. Dong Y, Ni W, Chen WJ, Wan B, Zhao GX, Shi ZQ, et al. Spectrum and classification of ATP7B variants in a large cohort of Chinese patients with Wilson’s disease guides genetic diagnosis. Theranostics 2016, 6: 638–649.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Liang XL, Yang RM, Wu ZY, Wang N, Li XH, Wang X. Diagnosis and treatment guidelines of Wilson disease. Chin J Neurol 2008, 41: 566–569.

    Google Scholar 

  5. Zhang YD, Yang RM. Therapeutic assessment of dimercaptosuccinic acid capsule in the treatment of hepatolenticular degeneration. New Drugs Clin Rem 1990, 9: 73–76 (in Chinese with English abstract).

    CAS  Google Scholar 

  6. Wu ZY, Lin MT, Murong SX, Wang N. Molecular diagnosis and prophylactic therapy for presymptomatic Chinese patients with Wilson disease. Arch Neurol 2003, 60: 737–741.

    Article  PubMed  Google Scholar 

  7. Ni W, Dong QY, Zhang Y, Wu ZY. Zinc monotherapy and a low-copper diet are beneficial in patients with Wilson disease after liver transplantation. CNS Neurosci Ther 2013, 19: 905–907.

    Article  CAS  PubMed  Google Scholar 

  8. Zhang YC. Research of hepatolenticular degeneration in the past 10 years. Zhonghua Shen Jing Jing Shen Ke Za Zhi 1959, 5: 326–327 (in Chinese).

    Google Scholar 

  9. Ferenci P, Czlonkowska A, Stremmel W, Houwen R, Rosenberg W, Schilsky M, et al. EASL clinical practice guidelines: Wilson’s disease. J Hepatol 2012, 56: 671–685.

    Article  Google Scholar 

  10. Abuduxikuer K, Li LT, Qiu YL, Wang NL, Wang JS. Wilson disease with hepatic presentation in an eight-month-old boy. World J Gastroenterol 2015, 21: 8981–8984.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hui J, Yuen YP, Chow CM, Chong J, Chiang G, Cheung CK, et al. Isolated persistent elevation of alanine transaminase for early diagnosis of pre-symptomatic Wilson’s disease in Chinese children. World J Pediatr 2013, 9: 361–364.

    Article  CAS  PubMed  Google Scholar 

  12. Lin LJ, Wang DX, Ding NN, Lin Y, Jin Y, Zheng CQ. Comprehensive analysis on clinical features of Wilson’s disease: an experience over 28 years with 133 cases. Neurol Res 2014, 36: 157–163.

    Article  CAS  PubMed  Google Scholar 

  13. Wu ZY, Zhang Y, Sun YM. Metabolic Disorder of Neurogenetic Disease. Shanghai: Science and Technology Press of Shanghai, 2014: 799–830.

    Google Scholar 

  14. Wu ZY, Murong SX, Chen SR. Wilson disease starting with psychiatric disorder. Chin J Birth Health Heredity 1997, 5: 97–98.

    Google Scholar 

  15. Huo LJ, Liao RR, Chen XM. Ophthalmic manifestations of Wilson’s disease. Chin J Ophthalmol 2008, 44: 128–130.

    Google Scholar 

  16. Li XH, Lu Y, Ling Y, Fu QC, Xu J, Zang GQ, et al. Clinical and molecular characterization of Wilson’s disease in China: identification of 14 novel mutations. BMC Med Genet 2011, 12: 6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Roberts EA, Schilsky ML. Diagnosis and treatment of Wilson disease: an update. Hepatology 2008, 47: 2089–2111.

    Article  CAS  PubMed  Google Scholar 

  18. Huang L, Li XH, Liang XL. Correlation between the findings by MRI in brain of Wilson disease and clinical manifestations. J Apoplexy Nerv Dis 2011, 28: 216–219.

    Google Scholar 

  19. Tang YB, Lu Q, Huang JJ, Yuan NP. MRI diagnosis of brain with hepatolenticular degeneration. J Clin Radiol 2008, 27: 1454–1456.

    Google Scholar 

  20. Yu XE, Yang RM. 132 cases brain MR imaging of hepatolenticular degeneration. J Apoplexy Nerv Dis 2007, 24: 30–34.

    CAS  Google Scholar 

  21. Wang ZB, Liu B, Liu HQ, Li DL, Wang XD. MRI features of brain with hepatolenticular degeneration in adults. Chin J CT MRI 2014, 12: 37–39.

    CAS  Google Scholar 

  22. Yang JJ, Li XH, Yang RM, Yu XE, Yu CL, Qian YF, et al. Susceptibility-Weighted Imaging manifestations in the brain of Wilson’s disease patients. PLoS One 2015, 10: e0125100.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Zhang YC, Qin ZJ, Zou HW. Observation of 25 patients with hepatolenticular degeneration. Zhonghua Shen Jing Jing Shen Ke Za Zhi 1957, 1: 45–59 (in Chinese).

    Google Scholar 

  24. Reilly M, Daly L, Hutchinson M. An epidemiological study of Wilson’s disease in the Republic of Ireland. J Neurol Neurosurg Psychiatry 1993, 56: 298–300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Coffey AJ, Durkie M, Hague S, McLay K, Emmerson J, Lo C, et al. A genetic study of Wilson’s disease in the United Kingdom. Brain 2013, 136: 1476–1487.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Gialluisi A, Incollu S, Pippucci T, Lepori MB, Zappu A, Loudianos G, et al. The homozygosity index (HI) approach reveals high allele frequency for Wilson disease in the Sardinian population. Eur J Hum Genet 2013, 21: 1308–1311.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Hu WB, Han YZ, Yang RM, Cheng N, Xue BC, Sun DY, et al. Epidemiological investigation on hepatolenticular degeneration of Han population in Jinzhai county and Lixin county, Anhui province: report of a family pedigree. Anhui Med J 2012, 33: 734–737 (in Chinese with English abstract).

    Google Scholar 

  28. Park HD, Ki CS, Lee SY, Kim JW. Carrier frequency of the R778L, A874V, and N1270S mutations in the ATP7B gene in a Korean population. Clin Genet 2009, 75: 405–407.

    Article  CAS  PubMed  Google Scholar 

  29. Mak CM, Lam CW, Tam S, Lai CL, Chan LY, Fan ST, et al. Mutational analysis of 65 Wilson disease patients in Hong Kong Chinese: identification of 17 novel mutations and its genetic heterogeneity. J Hum Genet 2008, 53: 55–63.

    Article  CAS  PubMed  Google Scholar 

  30. Wu ZY, Wang N, Lin MT, Fang L, Murong SX. Detection and analysis of mutations in Chinese patients with Wilson disease. Chin J Neurol 2001, 34: 152–156 (in Chinese with English abstract).

    CAS  Google Scholar 

  31. Wu ZY, Wang N, Lin MT, Fang L, Murong SX. Genotype-phenotype correlation of patients with Wilson disease in Chinese population. Chin Med J 2003, 83: 309–311.

    CAS  Google Scholar 

  32. Liu XQ, Zhang YF, Liu TT, Hsiao KJ, Zhang JM, Gu XF, et al. Correlation of ATP7B genotype with phenotype in Chinese patients with Wilson disease. World J Gastroenterol 2004, 10: 590–593.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Zhu M, Dong Y, Ni W, Wu ZY. Defective roles of ATP7B missense mutations in cellular copper tolerance and copper excretion. Mol Cell Neurosci 2015, 67: 31–36.

    Article  CAS  PubMed  Google Scholar 

  34. Zhu M, Ni W, Dong Y, Wu ZY. EGFP tags affect cellular localization of ATP7B mutants. CNS Neurosci Ther 2013, 19: 346–351.

    Article  CAS  PubMed  Google Scholar 

  35. Huang F, Liang XL, Wang Y, Xu PY, Yang CS, Yan ZW. Study on correlation between gene Arg778Leu mutation and clinical manifestation in Wilson’ s disease. Chin J Neurol 2000, 33: 290–291 (in Chinese with English abstract).

    CAS  Google Scholar 

  36. Lu Y, Wang JS, Yu H, Wang XH. Correlation of clinical features of Wilson’s disease with ATP7B gene mutation in Children. Chin J Evid Based Pediatr 2013, 8: 346–351 (in Chinese with English abstract).

    Google Scholar 

  37. 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: 165–173.

    Article  Google Scholar 

  38. Materia S, Cater MA, Klomp LW, Mercer JF, La Fontaine S. Clusterin and COMMD1 independently regulate degradation of the mammalian copper ATPases ATP7A and ATP7B. J Biol Chem 2012, 287: 2485–2499.

    Article  CAS  PubMed  Google Scholar 

  39. 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: 629–634.

    Article  CAS  Google Scholar 

  40. Wu ZY, Zhao GX, Chen WJ, Wang N, Wan B, Lin MT, et al. 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 2006, 84: 438–442.

    Article  CAS  PubMed  Google Scholar 

  41. Hung IH, Suzuki M, Yamaguchi Y, Yuan DS, Klausner RD, Gitlin JD. Biochemical characterization of the Wilson disease protein and functional expression in the yeast Saccharomyces cerevisiae. J Biol Chem 1997, 272: 21461–21466.

    Article  CAS  PubMed  Google Scholar 

  42. Chen C, Shen B, Xiao JJ, Wu R, Duff Canning SJ, Wang XP. Currently clinical views on genetics of Wilson’s disease. Chin Med J (Engl) 2015, 128: 1826–1830.

    Article  Google Scholar 

  43. Wu ZY, Wang N, Murong SX. Construction of site-directed mutant variants of ATP7B in vitro and their expression. Chin J Neurol 2003, 36: 339–342 (in Chinese with English abstract).

    CAS  Google Scholar 

  44. Yang CS, Liang XL, Li JY, Yan ZW, Huang F. Effect of the mutation of promoter region in Wilson disease ATP7B gene on the expression of reporter gene. Chin J Med Genet 2005, 22: 566–568 (in Chinese with English abstract).

    CAS  Google Scholar 

  45. Diao SP, Hong MF, Huang YQ, Wei ZS, Su QX, Peng ZX, et al. Identification and characterization of a novel splice-site mutation in the Wilson disease gene. J Neurol Sci 2014, 345: 154–158.

    Article  CAS  PubMed  Google Scholar 

  46. Wan L, Tsai CH, Hsu CM, Huang CC, Yang CC, Liao CC, et al. Mutation analysis and characterization of alternative splice variants of the Wilson disease gene ATP7B. Hepatology 2010, 52: 1662–1670.

    Article  CAS  PubMed  Google Scholar 

  47. Cheng N, Wang X, Yu X, Zhou Z, Gao M, Rao R, et al. Clinical and genetic study of Wilson’s disease in affected twins and siblings. Chin J Med Genet 2013, 30: 261–265 (in Chinese with English abstract).

    CAS  Google Scholar 

  48. Huster D. Wilson disease. Best Pract Res Clin Gastroenterol 2010, 24: 531-539.

    Article  CAS  PubMed  Google Scholar 

  49. Koopman WJ, Nijtmans LG, Dieteren CE, Roestenberg P, Valsecchi F, Smeitink JA, et al. Mammalian mitochondrial complex I: biogenesis, regulation, and reactive oxygen species generation. Antioxid Redox Signal 2010, 12: 1431–1470.

    Article  CAS  PubMed  Google Scholar 

  50. Zischka H, Lichtmannegger J, Schmitt S, Jägemann N, Schulz S, Wartini D, et al. Liver mitochondrial membrane crosslinking and destruction in a rat model of Wilson disease. J Clin Invest 2011, 121: 1508–1518.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Dong Y, Shi SS, Chen S, Ni W, Zhu M, Wu ZY. The discrepancy between the absence of copper deposition and the presence of neuronal damage in the brain of Atp7b(-/-) mice. Metallomics 2015, 7: 283–288.

    Article  CAS  PubMed  Google Scholar 

  52. Zhang JW, Liu JX, Hou HM, Chen DB, Feng L, Wu C, et al. Effects of tetrathiomolybdate and penicillamine on brain hydroxyl radical and free copper levels: a microdialysis study in vivo. Biochem Biophys Res Commun 2015, 458: 82–85.

    Article  CAS  PubMed  Google Scholar 

  53. Roberts EA, Schilsky ML. A practice guideline on Wilson disease. Hepatology 2003, 37: 1475–1492.

    Article  PubMed  Google Scholar 

  54. Xu SQ, Li XF, Zhu HY, Liu Y, Fang F, Chen L. Clinical efficacy and safety of chelation treatment with typical penicillamine in cross combination with DMPS repeatedly for Wilson’s disease. J Huazhong Univ Sci Technolog Med Sci 2013, 33: 743–747.

    Article  CAS  PubMed  Google Scholar 

  55. Yang RM, Cheng N. Observation on short-term effect and follow-up of integrative medicine in treating 198 patients with hepatolenticular degeneration. Chin J Integr Trad West Med 2002, 22: 657–659 (in Chinese with English abstract).

    Google Scholar 

  56. Hu JY, Yang RM, Han YZ, Hong MF, Wang X, Li K, et al. The clinical study of six antidotes against heavy metal poisoning in Wilson’ s disease. Anhui Med J 2004, 25: 361–365 (in Chinese with English abstract).

    Google Scholar 

  57. Li WJ, Wang JF, Wang XP. Wilson’s disease: Update on integrated chinese and western medicine. Chin J Integr Med 2013, 19: 233–240 (in Chinese with English abstract).

    Article  PubMed  Google Scholar 

  58. Tang QQ, Yang RM, Han YZ, Ren MS, Hong MF, Wang XP. Effect of gandou decoction on copper metabolism of skin fibroblast of hepatolenticular degeneration model. Chin J Integr Trad West Med 2000, 20: 37–39 (in Chinese with English abstract).

    CAS  Google Scholar 

  59. Xue BC, Yang RM, Hu JY, Han YZ, Wang JH. Effect of Gandou Decoction IV combined with short-term decoppering therapy with sodium dimercapto-sulphonate on serum indexes of hepatic fibrosis in patients with Wilson’ s disease. Chin J Integr Trad West Med 2007, 27: 785–788 (in Chinese with English abstract).

    Google Scholar 

  60. Wang Y, Xie CL, Fu DL, Lu L, Lin Y, Dong QQ, et al. 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: 143–154.

    Article  CAS  PubMed  Google Scholar 

  61. Huang F, Yu ZG, Liang XL. Therapeusis for Wilson’s disease accomplicated with splenosis-16 cases with splenectomization analysis. Chin J Nervous Mental Dis 2000, 26: 6–8 (in Chinese with English abstract).

    Google Scholar 

  62. Cheng Q, He SQ, Gao D, Lei B, Long X, Liang HF, et al. Early application of auxiliary partial orthotopic liver transplantation in murine model of Wilson disease. Transplantation 2015, 99: 2317–2324.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This review was supported by the National Natural Science Foundation of China (81125009).

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Authors and Affiliations

  1. Department of Neurology and Research Center of Neurology in the Second Affiliated Hospital, and the Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, 310009, China

    Juan-Juan Xie & Zhi-Ying Wu

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Correspondence to Zhi-Ying Wu.

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Xie, JJ., Wu, ZY. Wilson’s Disease in China. Neurosci. Bull. 33, 323–330 (2017). https://doi.org/10.1007/s12264-017-0107-4

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