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Biochemical genetics
Apr, 2025;63 (2): 1198-1218.

Clinical and Molecular Spectrum of Wilson Disease in the Arab World: A Systematic Review.

Halima Benzine, Saida Lhousni, Maria Rkain, Meryem Ouarzane, Redouane Boulouiz, Mohammed Bellaoui, Majida Charif
Author Information
  1. Halima Benzine: Genetics Unit, Medical Sciences Research Laboratory, Faculty of Medicine and Pharmacy, University Mohammed Premier, Oujda, Morocco.
  2. Saida Lhousni: Genetics Unit, Medical Sciences Research Laboratory, Faculty of Medicine and Pharmacy, University Mohammed Premier, Oujda, Morocco.
  3. Maria Rkain: Department of Pediatrics, Faculty of Medicine and Pharmacy, Mohammed VI University Hospital Center, University Mohammed Premier, Oujda, Morocco.
  4. Meryem Ouarzane: Genetics Unit, Medical Sciences Research Laboratory, Faculty of Medicine and Pharmacy, University Mohammed Premier, Oujda, Morocco.
  5. Redouane Boulouiz: Genetics Unit, Medical Sciences Research Laboratory, Faculty of Medicine and Pharmacy, University Mohammed Premier, Oujda, Morocco.
  6. Mohammed Bellaoui: Genetics Unit, Medical Sciences Research Laboratory, Faculty of Medicine and Pharmacy, University Mohammed Premier, Oujda, Morocco. bmbellaoui@gmail.com. ORCID
  7. Majida Charif: Genetics Unit, Medical Sciences Research Laboratory, Faculty of Medicine and Pharmacy, University Mohammed Premier, Oujda, Morocco. ma.charif@ump.ac.ma.
PMID: 39922954 DOI: 10.1007/s10528-025-11042-1

Abstract

Wilson Disease is a rare monogenic disease characterized by copper overload in various organs, mainly the liver, the brain and the eyes. It has a prevalence ranging between 1/30,000 and 1/50,000, and it is caused by pathogenic variants in the ATP7B gene, which encodes a copper-transporting ATPase essential for regulating liver copper levels by directing copper to the secretory pathway and exporting excess copper into bile. It is a fatal disease if left untreated; however early diagnosis and effective treatment enable patient's outcome improvement. Unfortunately, in the Arab world there is no collective data on Wilson Disease. This systematic review presents an explicit overview on the clinical and molecular spectrum of Wilson Disease in the Arab world. A literature search was conducted on five databases from their inception until April 2024, using a combination of words related to the genetics of Wilson Disease in the Arab world. The search resulted in 48 relevant studies carried out in 13 Arab countries, in which 802 Wilson Disease patients were reported, with a high rate of consanguinity, and a slight male predominance. Hepatic presentations were the most frequent features in patients, and a total of 92 variants were identified with a detection rate of 61.2%. Genotype-phenotype correlations were not established for the majority of variants. This review revealed a clinical and molecular heterogeneity of Wilson Disease in the Arab world. Efforts from health authorities, clinicians and geneticists are recommended to improve diagnosis, reduce disease incidence and give more insights into the present-day understanding of Wilson Disease in the Arab world.

Keywords

ATP7B gene Arab world Clinical spectrum Molecular spectrum Wilson disease

References

  1. Abbassi N, Bourrahouat A, Bedoya EC, Pagan C, Qabli ME, Maidoumi S, Belmalih A, Guillaud O, Kissani N, Abkari A, Chahid I, Rafai MA, Mouane N, Kriouile Y, Aidi S, Hida M, Idrissi ML, Belahsen MF, Abkari ME, Rkain M, Ismaili Z, Sedki A, Bost M, Aboussair N, Lachaux A (2024) Phenotype and molecular characterization of Wilson’s disease in Morocco. Clin Res Hepatol Gastroenterol 48:102335 [PMID: 38588792]
  2. Abdelghaffar TY, Elsayed SM, Elnaghy S, Shadeed A, Elsobky ES, Schmidt H (2011) Phenotypic and genetic characterization of a cohort of pediatric Wilson disease patients. BMC Pediatr 11:1–11
  3. Abdelmoula N (2021) Toxic accumulation of copper and neuropsychiatric symptoms due to a familial tunisian compound heterozygous ATP7B missense mutation [abstract]. Eur Psychiatry 64:S717–S718 [>PMCID: ]
  4. Ahmad A, Torrazza-Perez E, Schilsky ML (2017) Liver transplantation for Wilson disease. Handb Clin Neurol 142:193–204 [PMID: 28433103]
  5. Al-Jumah M, Majumdar R, Al-Rajeh S, Awada A, Al-Zaben A, Al-Traif I, Al-Jumah A, Rehana Z (2004) A clinical and genetic study of 56 Saudi Wilson disease patients: identification of Saudi-specific mutations. Eur J Neurol 11:121–124 [PMID: 14748773]
  6. Alkhouri N, Gonzalez-Peralta RP, Medici V (2023) Wilson disease: a summary of the updated AASLD Practice Guidance. Hepatol Commun 7:e0150 [PMID: 37184530]
  7. Al-Tobi M, Kashoob M, Joshi S, Bayoumi R (2011) A novel splice-site allelic variant is responsible for Wilson Disease in an Omani family. Sultan Qaboos Univ Med J 11:357 [PMID: 22087377]
  8. Barada K, el Haddad A, Katerji M, Jomaa M, Usta J (2017) Wilson’s disease in Lebanon and regional countries: homozygosity and hepatic phenotype predominance. World J Gastroenterol 23:6715 [PMID: 29085216]
  9. Beinhardt S, Leiss W, Stättermayer AF, Graziadei I, Zoller H, Stauber R, Maieron A, Datz C, Steindl-Munda P, Hofer H (2014) Long-term outcomes of patients with Wilson disease in a large Austrian cohort. Clin Gastroenterol Hepatol 12:683–689 [PMID: 24076416]
  10. Bhattacharya K, Thankappan B (2022) Wilson’s disease update: an Indian perspective. Ann Indian Acad Neurol 25:43 [PMID: 35342245]
  11. Blomhoff R, Andersen R, Arnesen EK, Christensen JJ, Eneroth H, Erkkola M, Gudanaviciene I, Halldórsson ÞI, Høyer-Lund A, Lemming EW (2023) Nordic nutrition recommendations 2023: integrating environmental aspects. Nordisk Ministerråd
  12. Bost M, Lachaux A, Accominotti M, Vandenberghe A (1999) Mutation screening and genotype-phenotype correlation in 32 families with Wilson disease. J Trace Elements Exp Med 12:321–329
  13. Botigué LR, Henn BM, Gravel S, Maples BK, Gignoux CR, Corona E, Atzmon G, Burns E, Ostrer H, Flores C (2013) Gene flow from North Africa contributes to differential human genetic diversity in southern Europe. Proc Natl Acad Sci 110:11791–11796 [PMID: 23733930]
  14. Bull PC, Thomas GR, Rommens JM, Forbes JR, Cox DW (1993) The Wilson disease gene is a putative copper transporting P–type ATPase similar to the Menkes gene. Nat Genet 5:327–337 [PMID: 8298639]
  15. Cai L, Huang X, Ye Y, Yang D, Xie L, Fu D, Peng L, Zhou D, Liao J (2023) Role of gender and age in features of Wilson’s disease. Front Neurol 14:1176946 [PMID: 37475745]
  16. Chanpong A, Dhawan A (2022) Wilson disease in children and young adults-state of the art. Saudi J Gastroenterol 28:21 [PMID: 35042319]
  17. Chappuis P, Callebert J, Quignon V, Woimant F, Laplanche J-L (2007) Late neurological presentations of Wilson disease patients in French population and identification of 8 novel mutations in the ATP7B gene. J Trace Elem Med Biol 21:37–42 [PMID: 17317524]
  18. Choe EJ, Choi JW, Kang M, Lee YK, Jeon HH, Park BK, Won SY, Cho YS, Seo JH, Lee CK (2020) A population-based epidemiology of Wilson’s disease in South Korea between 2010 and 2016. Sci Rep 10:14041 [PMID: 32820224]
  19. Cocoş R, Şendroiu A, Schipor S, Bohîlţea LC, Şendroiu I, Raicu F (2014) Genotype-phenotype correlations in a mountain population community with high prevalence of Wilson’s disease: genetic and clinical homogeneity. PLoS ONE 9:e98520 [PMID: 24897373]
  20. Coffey AJ, Durkie M, Hague S, McLay K, Emmerson J, Lo C, Klaffke S, Joyce CJ, Dhawan A, Hadzic N (2013) A genetic study of Wilson’s disease in the United Kingdom. Brain 136:1476–1487 [PMID: 23518715]
  21. Couchonnal E, Bouchard S, Sandahl TD, Pagan C, Lion-François L, Guillaud O, Habes D, Debray D, Lamireau T, Broué P (2021) ATP7B variant spectrum in a French pediatric Wilson disease cohort. Eur J Med Genet 64:104305 [PMID: 34400371]
  22. Cumings J (1948) The copper and iron content of brain and liver in the normal and in hepato-lenticular degeneration. Brain 71:410–415 [PMID: 18124738]
  23. Davies LP, Macintyre G, Cox DW (2008) New mutations in the Wilson disease gene, ATP7B: implications for molecular testing. Genet Test 12:139–145 [PMID: 18373411]
  24. Dhidah K, el Filali F, Naamane A, Khalifa HH, Aquaron R (2007) Maladie de wilson: étude clinique et biologie moléculaire. Immuno-Anal Biol Spécialisée 22:373–376
  25. Dmitriev O, Tsivkovskii R, Abildgaard F, Morgan CT, Markley JL, Lutsenko S (2006) Solution structure of the N-domain of Wilson disease protein: distinct nucleotide-binding environment and effects of disease mutations. Proc Natl Acad Sci 103:5302–5307 [PMID: 16567646]
  26. Dong Y, Wang R-M, Yang G-M, Yu H, Xu W-Q, Xie J-J, Zhang Y, Chen Y-C, Ni W, Wu Z-Y (2021) Role for biochemical assays and Kayser–Fleischer rings in diagnosis of Wilson’s disease. Clin Gastroenterol Hepatol 19:590–596 [PMID: 32485301]
  27. Dzieżyc-Jaworska K, Litwin T, Członkowska A (2019) Clinical manifestations of Wilson disease in organs other than the liver and brain. Ann Transl Med 7:S62 [PMID: 31179299]
  28. EFSA. 2023. Total copper intakes below new safe level. European Food SAfety authority. https://www.efsa.europa.eu/en/news/total-copper-intakes-below-new-safe-level . Accessed 11 Nov 2023
  29. el Goundali K, Chebabe M, Laamiri FZ, Hilali A (2022) The determinants of consanguineous marriages among the Arab population: a systematic review. Iran J Public Health 51:253 [PMID: 35866117]
  30. el Khattabi A, Seddik H, Fatihi J, Salaheddine H, Badaoui M, Amézyane T, Mahassine F, Ohayon V (2009) Anémie hémolytique récidivante révélatrice d’une maladie de Wilson (une nouvelle observation et revue de la littérature). Transfus Clin Biol 16:39–42 [PMID: 19329346]
  31. El-Karaksy H, Nomachi S, Esmat G, El-Serafy M, Kamel R, El-Ansary A, Refaat S, Tanaka K (2007) Letter to editor-equal outcome of living-related liver transplantation for Wilson’s disease from heterozygote and nonheterozygote donors: a report of a brother and sister. Indian J Med Sci 61:286–288 [PMID: 17478959]
  32. Elleuch N, Feki I, Turki E, Miladi M, Boukhris A, Damak M, Mhiri C, Chappuis E, Woimant F (2010) Nouvelle mutation du gène ATP7B responsable d’une maladie de Wilson avec atteinte neurologique sévère. Revue Neurologique 166:550–552 [PMID: 20036408]
  33. El-Mougy FA, Sharaf SA, Elsharkawy MM, Mandour IA, El-Essawy RA, Eldin AM, Helmy HM, Soliman DH, Selim LH, Sharafeldin HM (2014) Gene mutations in Wilson disease in Egyptian children: report on two novel mutations. Arab J Gastroenterol 15:114–118 [PMID: 25465132]
  34. Frikha R, Abdelmoula NB, Rebai T (2013) Wilson disease, genotype and infertility: is there a correlation? Endocrine 44:266–267 [PMID: 23307056]
  35. Gao J, Brackley S, Mann JP (2019) The global prevalence of Wilson disease from next-generation sequencing data. Genet Med 21:1155–1163 [PMID: 30254379]
  36. Gromadzka G, Bendykowska M, Przybyłkowski A (2023) Wilson’s disease—genetic puzzles with diagnostic implications. Diagnostics 13:1287 [PMID: 37046505]
  37. Gul B, Firasat S, Tehreem R, Shan T, Afshan K (2022) Analysis of Wilson disease mutations in copper binding domain of ATP7B gene. PLoS ONE 17:e0269833 [PMID: 35763513]
  38. Hariz M, Amri F, Fitouri Z, Abroug S, Abdelmoula S, Chaabouni M, Harbi A, Trabelsi M, Brini I, Ben becher S, Dridi M, Hachicha M, Triki A, Ammar B, Lakhoua R, Bousnina S, Barsaoui S, Essoussi S, Fathallah MD, Maherzi A (2004) P0368 Wilson disease: tunisian paediatric experience [abstract]. J Pediatric Gastroenterol Nutr. https://doi.org/10.1002/j.1536-4801.2004.tb12798.x [DOI: 10.1002/j.1536-4801.2004.tb12798.x]
  39. Hawsawi Y (2022) Novel variants associated with Wilson dis-ease in Saudi families. J Gstro Hepato 8:1–8
  40. Huang C, Fang M, Xiao X, Gao Z, Wang Y, Gao C (2022) Genetic studies discover novel coding and non-coding mutations in patients with Wilson’s disease in China. J Clin Lab Anal 36:e24459 [PMID: 35470480]
  41. Huong NTM, Hoa NPA, Ngoc ND, Mai NTP, Yen PH, vân Anh HT, Hoa G, Dien TM (2022) Mutation spectrum of ATP7B gene in pediatric patients with Wilson disease in Vietnam. Mol Genetics Metabol Rep 31:100861
  42. IEEE. 2015. The Saudi human genome program. https://www.embs.org/pulse/articles/the-saudi-human-genome-program/ . Accessed 28 Nov 2023
  43. Jopowicz A, Tarnacka B (2023) Neurological Wilson’s disease signs—hepatic encephalopathy or copper toxicosis? Diagnostics 13:893 [PMID: 36900037]
  44. Kalinsky H, Funes A, Zeldin A, Pel-Or Y, Korostishevsky M, Gershoni-Baruch R, Farrer LA, Bonne-Tamir B (1998) Novel ATP7B mutations causing Wilson disease in several Israeli ethnic groups. Hum Mutat 11:145–151 [PMID: 9482578]
  45. Kamimura K (2023) Wilson’s disease: practical information for general physicians. Hepatobiliary Surg Nutr 12:598 [PMID: 37601004]
  46. Kasztelan-Szczerbinska B, Cichoz-Lach H (2021) Wilson’s disease: an update on the diagnostic workup and management. J Clin Med 10:5097 [PMID: 34768617]
  47. Kim JW, Kim JH, Seo JK, Ko JS, Chang JY, Yang HR, Kang KH (2013) Genetically confirmed Wilson disease in a 9-month old boy with elevations of aminotransferases. World J Hepatol 5:156 [PMID: 23556051]
  48. Kleine RT, Mendes R, Pugliese R, Miura I, Danesi V, Porta G (2012) Wilson’s disease: an analysis of 28 Brazilian children. Clinics 67:231–235 [PMID: 22473403]
  49. Kumar M, Gaharwar U, Paul S, Poojary M, Pandhare K, Scaria V, Bk B (2020) WilsonGen a comprehensive clinically annotated genomic variant resource for Wilson’s disease. Sci Rep 10:9037 [PMID: 32493955]
  50. Lafhal K, Sabir E-S, Hakmaoui A, Hammoud M, Aimrane A, Najeh S, Assiri I, Berrachid A, Imad N, Boujemaa CA (2023) Clinical, biochemical and molecular characterization of Wilson’s disease in Moroccan patients. Mol Genetics Metabol Rep 36:100984
  51. League of Arab States. 2023. http://www.lasportal.org/ar/Pages/default.aspx . Accessed 12 Nov 2023
  52. Li X-H, Lu Y, Ling Y, Fu Q-C, Xu J, Zang G-Q, Zhou F, De-Min Y, Han Y, Zhang D-H (2011) Clinical and molecular characterization of Wilson’s disease in China: identification of 14 novel mutations. BMC Med Genet 12:1–13
  53. Li M, Ma J, Wang W, Yang X, Luo K (2021) Mutation analysis of the ATP7B gene and genotype–phenotype correlation in Chinese patients with Wilson disease. BMC Gastroenterol 21:1–21 [PMID: 33407176]
  54. Li Y, Liang J, Chen Y, Wang Y (2023) The mechanism of copper homeostasis and its role in disease. iLABMED 1:109–120
  55. Lin L-J, Wang D-X, Ding N-N, Lin Y, Jin Y, Zheng C-Q (2014) Comprehensive analysis on clinical features of Wilson’s disease: an experience over 28 years with 133 cases. Neurol Res 36:157–163 [PMID: 24107488]
  56. Linder MC (2020) Copper homeostasis in mammals, with emphasis on secretion and excretion: a review. Int J Mol Sci 21:4932 [PMID: 32668621]
  57. Litwin T, Gromadzka G, Członkowska A (2012) Gender differences in Wilson’s disease. J Neurol Sci 312:31–35 [PMID: 21917273]
  58. Litwin T, Dusek P, Szafrański T, Dzieżyc K, Członkowska A, Rybakowski JK (2018) Psychiatric manifestations in Wilson’s disease: possibilities and difficulties for treatment. Therap Adv Psychopharmacol 8:199–211
  59. Liu M, Jin M, Chen X, Wan B, Guo Y, Sheng M, Chen L, Zhao L, Huang D, Li Y (2018) ATP7B mutation detection and pathogenicity analysis: one atypical case of Wilson’s disease with adrenocortical insufficiency. J Mol Neurosci 64:20–28 [PMID: 29181760]
  60. Majarian TV (2014) Effect of copper chelators on ferroxidase and iron binding proteins: implications on Wilson Disease, Thesis, Dissertation. American University of Beirut
  61. Majumdar R, Al-Jumah M, Al-Rajeh S, Fraser M, Al-Zaben A, Awada A, Al-Traif I, Paterson M (2000) A novel deletion mutation within the carboxyl terminus of the copper-transporting ATPase gene causes Wilson disease. J Neurol Sci 179:140–143 [PMID: 11054498]
  62. Majumdar R, Al-Jumah M, Fraser M (2003) 4193delC, a common mutation causing Wilson’s disease in Saudi Arabia: rapid molecular screening of patients and carriers. Mol Pathol 56:302 [PMID: 14514926]
  63. Majumdar R, Al-Jumah M, Zaidan R (2004) A rare homozygous missense mutation in ATP7B exon 19 in a case of Wilson disease. Eur Neurol 51:52–54 [PMID: 14639035]
  64. Mak CM, Lam C-W, Tam S, Lai C-L, Chan L-Y, Fan S-T, Lau Y-L, Lai J-Y, Yuen P, Hui J (2008) Mutational analysis of 65 Wilson disease patients in Hong Kong Chinese: identification of 17 novel mutations and its genetic heterogeneity. J Hum Genet 53:55–63 [PMID: 18034201]
  65. Mariño Z, Berenguer M, Peña-Quintana L, Olveira A, Miralpeix A, Sastre I, Reyes-Domínguez A, Castillo P, García-Solà C, Bono A (2023) Health-related quality of life in patients living with Wilson Disease In Spain: a cross-sectional observational study. J Clin Med 12:4823 [PMID: 37510937]
  66. Medici V, Lasalle JM (2019) Genetics and epigenetic factors of Wilson disease. Ann Transl Med 7:S58 [PMID: 31179295]
  67. Merle U, Schaefer M, Ferenci P, Stremmel W (2007) Clinical presentation, diagnosis and long-term outcome of Wilson’s disease: a cohort study. Gut 56(1):115–120 [PMID: 16709660]
  68. Nayagam JS, Jeyaraj R, Foskett P, Dhawan A, Ala A, Joshi D, Bomford A, Thompson RJ (2023) ATP7B genotype and chronic liver disease treatment outcomes in Wilson disease: worse survival with loss-of-function variants. Clin Gastroenterol Hepatol 21:1323-1329.e4 [PMID: 36096368]
  69. Nilles C, Obadia MA, Sobesky R, Dumortier J, Guillaud O, Laurencin C, Moreau C, Vanlemmens C, Ory-Magne F, de Ledinghen V (2023) Diagnosis and outcomes of late-onset Wilson’s disease: a national registry-based study. Mov Disord 38:321–332 [PMID: 36573661]
  70. Patil M, Sheth KA, Krishnamurthy AC, Devarbhavi H (2013) A review and current perspective on Wilson disease. J Clin Exp Hepatol 3:321–336 [PMID: 25755520]
  71. Petrukhin K, Fischer S, Pirastu M, Tanzi R, Chernov I, Devoto M, Brzustowicz L, Cayanis E, Vitale E, Russo J (1993) Mapping, cloning and genetic characterization of the region containing the Wilson disease gene. Nat Genet 5:338–343 [PMID: 8298640]
  72. Pissaia A, Gouya H, Scatton O, Conti F, Calmus Y (2009) Regression of hypervascular nodules in a patient with wilson’s disease awaiting liver transplantation. J Transpl 2009:597371
  73. Polishchuk RS, Polishchuk EV (2019) From and to the Golgi–defining the Wilson disease protein road map. FEBS Lett 593:2341–2350 [PMID: 31408533]
  74. Poujois A, Woimant F (2019) Challenges in the diagnosis of Wilson disease. Ann Transl Med 7:S67 [PMID: 31179304]
  75. Rabeh RB, Essid L, Bouyahya O, Missaoui N, Yahyaoui S, Mazigh S, Boukthir S (2021) 267 Diagnosis and management of Wilson’s diseasein children: a Tunisian single-center experience [abstract]. BMJ Publishing Group Ltd
  76. Roy S, McCann CJ, Ralle M, Ray K, Ray J, Lutsenko S, Jayakanthan S (2020) Analysis of Wilson disease mutations revealed that interactions between different ATP7B mutants modify their properties. Sci Rep 10:13487 [PMID: 32778786]
  77. Sahli M, Zrhidri A, El-Kadiri Y, Cherkaoui Jaouad I, Meskini T, Sefiani A (2023) First application of next-generation sequencing in four families with Wilson disease in Morocco. Egypt J Med Hum Genet 24:54
  78. Sakhri M (2015) الوطن العربي – دراسة جيوسياسية. Academia. https://www.academia.edu/12228678/%D8%A7%D9%84%D9%88%D8%B7%D9%86_%D8%A7%D9%84%D8%B9%D8%B1%D8%A8%D9%8A_%D8%AF%D8%B1%D8%A7%D8%B3%D8%A9_%D8%AC%D9%8A%D9%88%D8%B3%D9%8A%D8%A7%D8%B3%D9%8A%D8%A9
  79. Salama E, Tarek F, Hala H, Ayman A, Manar A (2014) PS-075 genetic counseling of wilson disease in egyptian children: evaluation Of Atp7b gene mutation as a useful tool [abstract]. BMJ Publishing Group Ltd
  80. Schroeder SM, Matsukuma KE, Medici V (2021) Wilson disease and the differential diagnosis of its hepatic manifestations: a narrative review of clinical, laboratory, and liver histological features. Ann Transl Med 9:1394 [PMID: 34733946]
  81. Shagrani M, Burkholder J, Broering D, Abouelhoda M, Faquih T, El-Kalioby M, Subhani S, Goljan E, Albar R, Monies D (2017) Genetic profiling of children with advanced cholestatic liver disease. Clin Genet 92:52–61 [PMID: 28039895]
  82. Sheikh SM, Khair H (2013) Pregnancy with Wilson’s disease—a case report. Isra Med J 5:151–152
  83. Shribman S, Warner TT, Dooley JS (2019) Clinical presentations of Wilson disease. Ann Transl Med 7:S60 [PMID: 31179297]
  84. Singh P, Subedi B, Mahato D, Karn M (2024) Kayser-Fleischer rings: the pathognomonic for Wilson’s disease. Clin Case Rep 12:e8642 [PMID: 38464582]
  85. Sipilä JO, Hietala M, Kytö V, Kaasinen V (2020) Wilson’s Disease in Finland: A Nationwide Population-Based Study. Mov Disord 35:2323–2327 [PMID: 32618023]
  86. Sousa B, Magalhães P, Pinto A, Trindade E, Silva E, Ramos JP, Freitas S, Lopes S, Antunes H, Trindade Sr E (2023) Wilson’s disease: a prevalence study in a portuguese population. Cureus 15:e43718 [PMID: 37724235]
  87. Stremmel W, Weiskirchen R (2022) Wilson disease: more complex than just simply a copper overload condition? A narrative review. AME Med J. https://doi.org/10.18154/RWTH-2022-11374 [DOI: 10.18154/RWTH-2022-11374]
  88. Tadmouri GO, Nair P, Obeid T, Al-Ali MT, Al-Khaja N, Hamamy HA (2009) Consanguinity and reproductive health among Arabs. Reprod Health 6:1–9
  89. Tanzi R, Petrukhin K, Chernov I, Pellequer J, Wasco W, Ross B, Romano D, Parano E, Pavone L, Brzustowicz L (1993) The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene. Nat Genet 5:344–350 [PMID: 8298641]
  90. Tazin F, Kumar H, Orlang V (2022) Wilson’s disease manifestation in late adulthood: a case report and literature review. Cureus 14:e29797 [PMID: 36340556]
  91. Teebi AS, Teebi SA (2005) Genetic diversity among the Arabs. Community Genet 8:21–26 [PMID: 15767750]
  92. Temaj G, Nuhii N, Sayer J (2022) The impact of consanguinity on human health and disease with an emphasis on rare diseases. J Rare Dis 1:2
  93. Temtamy SA, Hussen DF (2017) Genetics and genomic medicine in Egypt: steady pace. Mol Genet Genomic Med 5:8 [PMID: 28116325]
  94. UNFPA (2023) https://arabstates.unfpa.org/ar . Accessed 12 Nov 2023
  95. Usta J, Wehbeh A, Rida K, El-Rifai O, Estiphan TA, Majarian T, Barada K (2014) 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 9:e109727 [PMID: 25390358]
  96. Wagner S, Brunet A-S, Bost M, Lachaux A, Broussolle E, Des Portes V, Lion-François L (2012) Maladie de Wilson, penser aux formes neurologiques chez l’enfant. Arch Pediatr 19:271–276 [PMID: 22261259]
  97. Wang L-H, Huang Y-Q, Shang X, Su Q-X, Xiong F, Yu Q-Y, Lin H-P, Wei Z-S, Hong M-F, Xu X-M (2011) Mutation analysis of 73 southern Chinese Wilson’s disease patients: identification of 10 novel mutations and its clinical correlation. J Hum Genet 56:660–665 [PMID: 21796144]
  98. Wang Z, Jin D, Zhou S, Dong N, Ji Y, An P, Wang J, Luo Y, Luo J (2023) Regulatory roles of copper metabolism and cuproptosis in human cancers. Front Oncol 13:1123420 [PMID: 37035162]
  99. Wilson SK (1912) Progressive lenticular degeneration. Br Med J 2:1645 [>PMCID: ]
  100. Yang G-M, Xu L, Wang R-M, Tao X, Zheng Z-W, Chang S, Ma D, Zhao C, Dong Y, Wu S (2023) Structures of the human Wilson disease copper transporter ATP7B. Cell Rep 42:112417 [PMID: 37074913]
  101. Zafaran M (2023) The role of stigma in the barriers to mental health treatment in the arab culture
  102. Zali N, Mohebbi SR, Esteghamat S, Chiani M, Haghighi MM, Hosseini-Asl SM-K, Derakhshan F, Mohammad-Alizadeh A-H, Malek-Hosseini S-A, Zali MR (2011) Prevalence of ATP7B gene mutations in Iranian patients with Wilson disease. Hepat Mon 11:890–894 [PMID: 22308153]
  103. Zhang S, Yang W, Li X, Pei P, Dong T, Yang Y, Zhang J (2022) Clinical and genetic characterization of a large cohort of patients with Wilson’s disease in China. Transl Neurodegen 11:1–11
  104. Zhou J, Zhang Q, Zhao Y, Chen M, Zhou S, Cheng Y (2022) Early diagnosis of Wilson’s disease in children in southern China by using common parameters. Front Genet 13:788658 [PMID: 35222532]
  105. Zhu Q, Zhu K, Wang J, Bian W, Lu J (2019) Relationship between genetic mutations and clinical phenotypes in patients with Wilson disease. Medicine 98:e18284 [PMID: 31804371]

MeSH Term

Hepatolenticular Degeneration
Humans
Copper-Transporting ATPases
Arab World
Mutation
Copper

Chemicals

Copper-Transporting ATPases
ATP7B protein, human
Copper
Systematic Review Journal Article Review

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Created with Highcharts 10.0.0diseaseWilsonArabworldcoppervariantsspectrumliver000ATP7BgenediagnosisreviewclinicalmolecularsearchpatientsrateClinicalMolecularraremonogeniccharacterizedoverloadvariousorgansmainlybraineyesprevalenceranging1/301/50causedpathogenicencodescopper-transportingATPaseessentialregulatinglevelsdirectingsecretorypathwayexportingexcessbilefatalleftuntreatedhoweverearlyeffectivetreatmentenablepatient'soutcomeimprovementUnfortunatelycollectivedatasystematicpresentsexplicitoverviewliteratureconductedfivedatabasesinceptionApril2024usingcombinationwordsrelatedgeneticsresulted48relevantstudiescarried13countries802reportedhighconsanguinityslightmalepredominanceHepaticpresentationsfrequentfeaturestotal92identifieddetection612%Genotype-phenotypecorrelationsestablishedmajorityrevealedheterogeneityEffortshealthauthoritiescliniciansgeneticistsrecommendedimprovereduceincidencegiveinsightspresent-dayunderstandingSpectrumDiseaseWorld:SystematicReview

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