Late-onset Wilson’s disease
https://doi.org/10.30629/2658-7947-2026-31-2-43-50
Abstract
Background. Wilson’s disease (WD) is characterized by wide phenotypic heterogeneity and may manifest not only in childhood and young adulthood but also after 40 years of age, which complicates timely diagnosis and worsens prognosis.
Objective. To analyze the clinical, genetic, laboratory, and neuroimaging features of neurological forms of late-onset WD.
Methods. Ninety-eight patients with neurological WD who were followed at a neurological research center from 2016 to 2025 were examined. In 16 patients (16.3%), disease onset occurred after the age of 40. A retrospective analysis of clinical manifestations, copper metabolism parameters, liver function tests, brain MRI findings at disease onset, and DNA diagnostic results was performed. The findings were compared with those in patients with a typical age of onset.
Results. In late-onset WD, tremor and tremor–rigid forms were observed more frequently, with a predominance of tremor and parkinsonian features. Disturbances of copper metabolism were less pronounced. Compensated liver cirrhosis predominated, and putaminal involvement on MRI was less frequent. Molecular genetic analysis revealed that the known pathogenic ATP7B variant p.H1069Q was more frequently detected in the homozygous state (68.8%).
Conclusion. Late-onset WD has a distinct neurological and radiological profile and may closely mimic common adult-onset movement disorders. WD should be routinely considered in the differential diagnosis of extrapyramidal syndromes, even in patients over 40 years of age.
About the Authors
I. V. Minaev
Russian Research Center of Neurology and Neuroscience
Russian Federation
Russian Federation
Moscow
E. P. Nuzhnyi
Russian Research Center of Neurology and Neuroscience
Russian Federation
Russian Federation
Moscow
V. V. Poleshchuk
Russian Research Center of Neurology and Neuroscience
Russian Federation
Russian Federation
Moscow
S. N. Illarioshkin
Russian Research Center of Neurology and Neuroscience
Russian Federation
Russian Federation
Moscow
References
1. Poujois A, Woimant F. Wilson's disease: a 2017 update. Clinical Research in Hepatology and Gastroenterology. 2018;42(6):512– 520. https://doi.org/10.1016/j.clinre.2018.03.007
2. Yuan XZ, Yang RM, Wang XP. Management perspective of Wilson's disease: early diagnosis and individualized therapy. Current Neuropharmacology. 2021;19(4):465–485. https://doi.org/10.2174/1570159X18666200429233517
3. Bayazutdinova GM, Shchagina OA, Karunas AS, Vyalova NV, Sokolov AA, Polyakov AV. Spectrum of mutations in the ATP7B gene in Russian patients with Wilson's disease. Genetics (Genetica). 2019;55(12):1433–1441 (Russian). https://doi.org/10.1134/S0016675819120026
4. Gerner EA, Nazarov VD, Fedorova TF, Lapin SV, Pavlova TA, Novikov SA, Alekseeva TM, Emanuel VL, Panina EB. Clinical, laboratory and molecular genetic diagnostics of Wilson–Konovalov disease. Russian Neurological Journal (Rossiyskiy nevrologicheskiy zhurnal). 2019;24(3):10–18 (Russian). https://doi.org/10.30629/2658-7947-2019-24-3-10-18
5. Bandmann O, Weiss KH, Kaler SG. Wilson's disease and other neurological copper disorders. The Lancet Neurology.2015;14(1):103–113. https://doi.org/10.1016/S14744422(14)70190-5
6. Wilson DC, Phillips MJ, Cox DW, Roberts EA. Severe hepatic Wilson's disease in preschool-aged children. Journal of Pediatrics. 2000;137(5):719–722. https://doi.org/10.1067/mpd.2000.108569
7. Członkowska A, Rodo M, Gromadzka G. Late onset Wilson's disease: therapeutic implications. Movement Disorders.2008;23(6):896–898. https://doi.org/10.1002/mds.21985
8. Nilles C, Obadia MA, Sobesky R, Desgranges B, Guillard O, Woimant F, et al. Diagnosis and outcomes of late-onset Wilson's disease: a national registry-based study. Movement Disorders. 2023;38:321–332. https://doi.org/10.1002/mds.29292
9. Yang W, Yang Y, Wang H, Wang J, Zhang S. Clinical and genetic characterization of patients with late onset Wilson's disease. npj Genomic Medicine. 2024;9:71. https://doi.org/10.1038/s41525-024-00459-z
10. Ferenci P, Członkowska A, Merle U, Ferenc S, Gromadzka G, Yurdaydin C, et al. Late-onset Wilson's disease. Gastroenterology. 2007;132:1294–1298. https://doi.org/10.1053/j.gastro.2007.02.057
11. Poleshchuk VV, Fedotova E.Yu., Ivanova-Smolenskaya IA. A case of hepatolenticular degeneration with neurological debut after 45 years. Diseases of the nervous system (Nervnye bolezni). 2012;2:40–44 (Russian).
12. Klocheva EG, Goldobin VV, Aleksandrov MV, Chistova IV, Popovskaya Ya.N., Zhukova MV. Late-onset Wilson–Konovalov disease (a clinical case). Medicinskij Alfavit. 2022;1(32):47–52 (Russian). https://doi.org/10.33667/2078-5631-2022-32-47-52
13. Dušek P, Smolinski L, Redzia-Ogrodnik B, Golebiowski M, Skowronska M, Poujois A, Laurencin C, Jastrzebska-Kurkowska I, Litwin T, Członkowska A. Semiquantitative scale for assessing brain MRI abnormalities in Wilson disease: a validation study. Movement Disorders. 2020;35(6):994–1001. https://doi.org/10.1002/mds.28018
14. Žigrai M, Vyskočil M, Tóthová A, Vereš P, Bluska P, Valkovič P. Late-onset Wilson's disease. Frontiers in Medicine (Front. Med.) 2020;7:26. https://doi.org/10.3389/fmed.2020.00026
15. Tazin F, Kumar H, Orlang V. Wilson's disease manifestation in late adulthood: a case report and literature review. Cureus. 2022;14(9):e29797. https://doi.org/10.7759/cureus.29797
16. Saibaba J, Gomathy SB, Sugumaran R, Narayan SK. Progressive supranuclear palsy or something more? Unveiling late-onset Wilson's disease. Annals of Indian Academy of Neurology. 2025 Dec 6. https://doi.org/10.4103/aian.aian_795_25
17. AlDhaleei W, AlAhmad M, Alhosani I. Wilson's disease presenting in late adult life. Case Reports in Gastroenterology.2021;15(1):142–146. https://doi.org/10.1159/000512422
18. Weitzman E, Pappo O, Weiss P, Frydman M, Haviv-Yadid Y, Ben Ari Z. Late-onset fulminant Wilson's disease: a case report and review of the literature. World Journal of Gastroenterology. 2014;20(46):17656–17660. https://doi.org/10.3748/wjg.v20.i46.17656
19. Stapelbroek JM, Bollen CW, Ploos van Amstel JK, van Erpecum KJ, van Hattum J, van den Berg LH, Klomp LW.J., Houwen RH.J. The H1069Q mutation in ATP7B is associated with late and neurologic presentation in Wilson disease: results of a meta-analysis. Journal of Hepatology. 2004;41(5):758–763. https://doi.org/10.1016/j.jhep.2004.07.017
20. Chang IJ, Hahn SH. The genetics of Wilson disease. In: Członkowska A, Schilsky ML. (eds). Handbook of Clinical Neurology. Vol. 142, pp. 19–34. Amsterdam: Elsevier; 2017. https://doi.org/10.1016/B978-0-444-63625-6.00003-3
21. Mihaylova V, Todorov T, Jelev H, Kotsev I, Angelova L, Kosseva O, Georgiev G, Ganeva R, Cherninkova S, Tankova L, Savov A, Tournev I. Neurological symptoms, genotype-phenotype correlations and ethnic-specifi c diff erences in Bulgarian patients with Wilson disease. The Neurologist. 2012;18(4):184–189. https://doi.org/10.1097/NRL.0b013e31825cf3b7
22. Ignatova TM, Solovyeva OV, Arion EA, Balashova MS, Rozina TP. Wilson–Konovalov disease in two sisters: diff erences in clinical course, successful therapy. Clinical Medicine (Klinicheskaya meditsina). 2016;94(1):70–73 (Russian). https://doi.org/10.18821/00232149-2016-94-1-70-73
23. Kluska A, Kulecka M, Litwin T, Dzieżyc K, Balabas A, Piatkowska M, Paziewska A, Dąbrowska M, Mikula M, Kamińska D, Wiernicka A, Socha P, Członkowska A, Ostrowski J. Whole-exome sequencing identifi es novel pathogenic variants across the ATP7B gene and some modifi ers of Wilson's disease phenotype. Liver International. 2019;39(1):177–186. https://doi.org/10.1111/liv.13967
24. Merico D, Spickett C, O'Hara M, Kakaradov B, Deshwar AG, Fradkin P, Gandhi S, Gao J, Grant S, Kron K, Schmitges FW, Shalev Z, Sun M, Verby M, Cahill M, Dowling JJ, Fransson J, Wienholds E, Frey BJ. ATP7B variant c.1934T > G p.Met645Arg causes Wilson disease by promoting exon 6 skipping. npj Genomic Medicine.2020;5:16. https://doi.org/10.1038/s41525-020-0123-6
25. Svetel M, Kozić D, Stefanova E, Semnic R, Dragasevic N, Kostic VS. Dystonia in Wilson's disease. Movement Disorders. 2001;16(4):719–723. https://doi.org/10.1002/mds.1118
26. Bandmann O, Weiss KH, Kaler SG. Wilson's disease and other neurological copper disorders. Lancet Neurology. 2015;14(1):103– 113. https://doi.org/10.1016/S1474-4422(14)70190-5
Review
For citations:
Minaev I.V., Nuzhnyi E.P., Poleshchuk V.V., Illarioshkin S.N. Late-onset Wilson’s disease. Russian neurological journal. 2026;31(2):43–50. (In Russ.) https://doi.org/10.30629/2658-7947-2026-31-2-43-50
Views:
100
JATS XML
Email this article 