The site of the Media Sphera Publishers contains materials intended solely for healthcare professionals.
By closing this message, you confirm that you are a certified medical professional or a student of a medical educational institution.

Login
EN
+7 (495) 482-4118
+7 (495) 482-0604
+8 800 250-18-12
  • (toll-free number for subscriptions)
    Mon-Fri from 10 a.m. to 6 p.m.

  • © 1998-2025
+7 (495) 482-43-29
EN
All journals
Journal
Year
Year
Search result: 0

Volynets G.V.

Pirogov Russian National Research Medical University

Nikitin A.V.

Pirogov Russian National Research Medical University;
Morozov Children’s City Clinical Hospital

Skvortsova T.A.

Pirogov Russian National Research Medical University;
Morozov Children’s City Clinical Hospital

Wilson’s Disease in children: challenges and prospects

Authors:

Volynets G.V., Nikitin A.V., Skvortsova T.A.

More about the authors

Journal: Russian Journal of Evidence-Based Gastroenterology. 2024;13(3): 80‑96

DOI: 10.17116/dokgastro20241303180

Read: 1689 times

Download PDF (RU)
Contact the author
Table of contents

WILSON’S DISEASE IN CHILDREN: CHALLENGES AND PROSPECTS
WILSON’S DISEASE IN CHILDREN: CHALLENGES AND PROSPECTS

To cite this article:

Volynets GV, Nikitin AV, Skvortsova TA. Wilson’s Disease in children: challenges and prospects. Russian Journal of Evidence-Based Gastroenterology. 2024;13(3):80‑96. (In Russ.)
https://doi.org/10.17116/dokgastro20241303180

Подписка 2026 Доказательная гастроэнтерология (Russian Journal of Evidence-Based Gastroenterology)
МСФ на ЯМ
Использование инфографики авторами научных работ
Close metadata
Recommended articles:
Modern view on the etiology of gallstone disease in children. Russian Journal of Evidence-Based Gastroenterology. 2024;(4):59-68
On the issue of the etiology of acute inflammatory pathology of the pharynx in children. Russian Bulletin of Otorhinolaryngology. 2024;(5):10-15
Dive­rse mani­festations of orbi­tal pseudotumor in a six-year-old child (case study). Russian Annals of Ophthalmology. 2024;(5):106-111
Epidemiology of suicidal beha­vior in children and adolescents worldwide. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;(11-2):16-26
Diagnosis of neuroinfections in children. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;(11-2):51-59
Modern approaches to diagnosis and treatment of syndrome of auto­nomic dysfunction in children. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;(11-2):66-75
Studying the possibility of using methods for asse­ssing expressive speech deve­lopmental diso­rders in children 3—6 years old. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;(11-2):103-109
Inte­rnal hernias stra­ngulated in mese­nteric openings in young children. Piro­gov Russian Journal of Surgery. 2024;(11):54-59
The effect of sevo­flurane and propofol on serum nuclear and mito­chondrial DNA in pediatric patients with craniosynostosis. Russian Journal of Anesthesiology and Reanimatology. 2024;(6):55-62
Problems of providing dental care to children using the example of the city of Chapaevsk, Samara region. Russian Journal of Operative Surgery and Clinical Anatomy. 2024;(4):35-42
Abstract:

Wilson’s disease (WD) is a rare autosomal recessive disorder of copper metabolism that primarily affects the liver and brain. In children, the hepatic phenotype of the disease predominates. Low awareness of the neuropsychiatric manifestations of WD in children leads to insufficient diagnosis of neurological forms. Managing children with WD requires a multidisciplinary approach involving hepatologists, geneticists, neurologists, and psychiatrists. This review aims to highlight the latest advances in the study of WD in children, discuss diagnostic challenges, and explore treatment prospects.

KEY POINTS

The article reviews recent advancements in understanding the hepatic and neuropsychiatric symptoms of WD in children and describes existing diagnostic and treatment challenges. The ATP7B gene, whose mutations cause WD, plays a key role in copper metabolism. Diagnosis of WD is based on a combination of clinical signs, biochemical tests, and genetic testing. Serum ceruloplasmin levels, urinary copper excretion, and hepatic copper content are primary biomarkers of the disease. WD treatment focuses on reducing copper levels in the body using chelating agents such as D-penicillamine and trientine dihydrochloride. Zinc is used to decrease copper absorption from the gastrointestinal tract. Liver transplantation is considered a treatment option in cases of severe hepatic failure.

CONCLUSIONS

WD requires early diagnosis and a multidisciplinary approach to patient management. Further research is needed to improve diagnostic and therapeutic strategies, including the development of new biomarkers and gene therapy. The importance of genetic counseling and family screening is emphasized for the timely identification and treatment of the disease. The authoritative information presented in the article contributes to raising awareness of WD in children and improving clinical practice.

Keywords:

Wilson’s disease
child
chelating agents
ceruloplasmin
gastroenterology

Authors:

Volynets G.V.

Pirogov Russian National Research Medical University

Nikitin A.V.

Pirogov Russian National Research Medical University;
Morozov Children’s City Clinical Hospital

Skvortsova T.A.

Pirogov Russian National Research Medical University;
Morozov Children’s City Clinical Hospital

Received:

20.05.2024

Accepted:

24.07.2024

Close metadata

References:

  1. 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
  2. Fernando M, van Mourik I, Wassmer E, Kelly D. Wilson disease in children and adolescents. Archives of Disease in Childhood. 2020;105(5):499-505.  https://doi.org/10.1136/archdischild-2018-315705
  3. Socha P, Janczyk W, Dhawan A, Baumann U, D’Antiga L, Tanner S, Iorio R, Vajro P, Houwen R, Fischler B, Dezsofi A, Hadzic N, Hierro L, Jahnel J, McLin V, Nobili V, Smets F, Verkade HJ, Debray D. Wilson’s Disease in Children: A Position Paper by the Hepatology Committee of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition. Journal of Pediatric Gastroenterology and Nutrition. 2018;66(2):334-344.  https://doi.org/10.1097/MPG.0000000000001787
  4. Członkowska A, Litwin T, Dusek P, Ferenci P, Lutsenko S, Medici V, Rybakowski JK, Weiss KH, Schilsky ML. Wilson disease. Nature Reviews. Disease Primers. 2018;4(1):21.  https://doi.org/10.1038/s41572-018-0018-3
  5. Mariño Z, Molera-Busoms C, Badenas C, Quintero-Bernabeu J, Torra M, Forns X, Artuch R. Benefits of using exchangeable copper and the ratio of exchangeable copper in a real-world cohort of patients with Wilson disease. Journal of Inherited Metabolic Disease. 2023;46(5):982-991.  https://doi.org/10.1002/jimd.12639
  6. Kaplan JH, Maryon EB. How mammalian cells acquire copper: an essential but potentially toxic metal. Biophysical Journal. 2016;110(1):7-13.  https://doi.org/10.1016/j.bpj.2015.11.025
  7. Roberts EA, Schilsky ML; American Association for Study of Liver Diseases (AASLD). Diagnosis and treatment of Wilson disease: an update. Hepatology. 2008;47(6):2089-2111. https://doi.org/10.1002/hep.22261
  8. Olivares M, Uauy R. Limits of metabolic tolerance to copper and biological basis for present recommendations and regulations. American Journal of Clinical Nutrition. 1996;63(5):846S-52S.  https://doi.org/10.1093/ajcn/63.5.846
  9. Sokol R, Silverman A. Copper metabolism and copper storage disorders in children. In: Suchy F, Sokol R, Balistreri W, Bezerra J, Mack C, Shneider B, eds Liver Disease in Children. 5th ed: Cambridge; 2021: 484-514.  https://doi.org/10.1017/9781108918978.028
  10. Rochford G, Molphy Z, Kavanagh K, McCann M, Devereux M, Kellett A, Howe O. Cu(ii) phenanthroline-phenazine complexes dysregulate mitochondrial function and stimulate apoptosis. Metallomics.2020;12:65-78.  https://doi.org/10.1039/c9mt00187e
  11. Shao J, Li M, Guo Z, Jin C, Zhang F, Ou C, Xie Y, Tan S, Wang Z, Zheng S, Wang X. TPP-related mitochondrial targeting copper (II) complex induces p53-dependent apoptosis in hepatoma cells through ROS-mediated activation of Drp1. Cell Communication and Signaling. 2019;17:149.  https://doi.org/10.1186/s12964-019-0468-6
  12. Członkowska A, Gromadzka G, Chabik G. Monozygotic female twins discordant for phenotype of Wilson’s disease. Movement Disorders. 2009;24(7):1066-1069. https://doi.org/10.1002/mds.22474
  13. Coffey AJ, Durkie M, Hague S, McLay K, Emmerson J, Lo C, Klaffke S, Joyce CJ, Dhawan A, Hadzic N, Mieli-Vergani G, Kirk R, Elizabeth Allen K, Nicholl D, Wong S, Griffiths W, Smithson S, Giffin N, Taha A, Connolly S, Gillett GT, Tanner S, Bonham J, Sharrack B, Palotie A, Rattray M, Dalton A, Bandmann O. A genetic study of Wilson’s disease in the United Kingdom. Brain. 2013;136(Pt 5):1476-1487. https://doi.org/10.1093/brain/awt035
  14. Community Research and Development Information Service. Final Report — EUROWILSON (Wilson Disease: Creating a European Clinical Database and designing multicentre randomised controlled clinical trials). Accessed March 12, 2024. https://www.cordis.europa.eu/publication/rcn/12737
  15. 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. Russian Journal of Genetics. 2019;55(12):1528-1535. https://doi.org/10.1134/S1022795419120020
  16. Chanpong A, Dhawan A.Wilson disease in children and young adults — State of the art. Saudi Journal of Gastroenterology. 2022; 28(1):21-31.  https://doi.org/10.4103/sjg.sjg_501_21
  17. 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 International. 2003;23(3): 139-142.  https://doi.org/10.1034/j.1600-0676.2003.00824.x
  18. Kelly DA. (Ed.). Diseases of the Liver and Biliary System in Children. Oxford: Wiley-Blackwell; 2017. https://doi.org/10.1002/9781119046936
  19. 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. Neurological Research. 2014;36(2): 157-163.  https://doi.org/10.1179/1743132813Y.0000000262
  20. Kerkar N, Rana A. Wilson Disease in Children. Clinics in Liver Disease. 2022;26(3):473-488.  https://doi.org/10.1016/j.cld.2022.03.008
  21. Roberts EA, Yap J. Nonalcoholic Fatty Liver Disease (NAFLD): Approach in the adolescent patient. Current Treatment Options in Gastroenterology. 2006;9(5):423-431.  https://doi.org/10.1007/BF02738532
  22. Yener S, Akarsu M, Karacanci C, Sengul B, Topalak O, Biberoglu K, Akpinar H. Wilson’s disease with coexisting autoimmune hepatitis. Journal of Gastroenterology and Hepatology. 2004;19(1): 114-116.  https://doi.org/10.1111/j.1440-1746.2004.03254.x
  23. Squires RH Jr, Shneider BL, Bucuvalas J, Alonso E, Sokol RJ, Narkewicz MR, Dhawan A, Rosenthal P, Rodriguez-Baez N, Murray KF, Horslen S, Martin MG, Lopez MJ, Soriano H, McGuire BM, Jonas MM, Yazigi N, Shepherd RW, Schwarz K, Lobritto S, Thomas DW, Lavine JE, Karpen S, Ng V, Kelly D, Simonds N, Hynan LS. Acute liver failure in children: The first 348 patients in the pediatric acute liver failure study group. Journal of Pediatrics. 2006;148(5):652-658.  https://doi.org/10.1016/j.jpeds.2005.12.051
  24. Zaccherini G, Weiss E, Moreau R. Acute on chronic liver failure: Defnitions, pathophysiology and principles of treatment. JHEP reports. 2020;3(1):100176. https://doi.org/10.1016/j.jhepr.2020.100176
  25. European Association for Study of Liver. EASL clinical practice guidelines: Wilson’s disease. Journal of Hepatology. 2012;56(3): 671-685.  https://doi.org/10.1016/j.jhep.2011.11.007
  26. Mak CM, Lam CW, Tam S. Diagnostic accuracy of serum ceruloplasmin in Wilson disease: determination of sensitivity and specificity by ROC curve analysis among ATP7B-genotyped subjects. Clinical Chemistry. 2008;54(8):1356-1362. https://doi.org/10.1373/clinchem.2008.103432
  27. Nicastro E, Ranucci G, Vajro P, Vegnente A, Iorio R. Re-evaluation of the diagnostic criteria for Wilson disease in children with mild liver disease. Hepatology. 2010;52(6):1948-1956. https://doi.org/10.1002/hep.23910
  28. Woimant F, Djebrani-Oussedik N, Poujois A. New tools for Wilson’s disease diagnosis: exchangeable copper fraction. Annals of Translational Medicine. 2019;7(Suppl 2):S70.  https://doi.org/10.21037/atm.2019.03.02
  29. Johncilla M, Mitchell KA. Pathology of the liver in copper overload. Seminars in Liver Disease. 2011;31(3):239-244.  https://doi.org/10.1055/s-0031-1286055
  30. Miyamura H, Nakanuma Y, Kono N. Survey of copper granules in liver biopsy specimens from various liver abnormalities other than Wilson’s disease and biliary diseases. Gastroenterologia Japonica. 1988;23(6):633-638.  https://doi.org/10.1007/BF02782948
  31. Lorincz MT. Neurologic Wilson’s disease. Annals of the New York Academy of Sciences. 2010;1184:173-187.  https://doi.org/10.1111/j.1749-6632.2009.05109.x
  32. Abdel Ghaffar TY, Elsayed SM, Elnaghy S, Shadeed A, Elsobky ES, Schmidt H. Phenotypic and genetic characterization of a cohort of pediatric Wilson disease patients. BMC Pediatrics. 2011;11:56.  https://doi.org/10.1186/1471-2431-11-56
  33. Bayram AK, Gümüş H, Arslan D, Özçora GK, Kumandaş S, Karacabey N, Canpolat M, Per H. Neurological features and management of Wilson disease in children: an evaluation of 12 cases. Turk Pediatri Arsivi. 2016;51(1):15-21.  https://doi.org/10.5152/TurkPediatriArs.2016.3080
  34. Rukunuzzaman M. Wilson’s disease in Bangladeshi children: analysis of 100 cases. Pediatric Gastroenterology, Hepatology & Nutrition. 2015;18(2):121-127.  https://doi.org/10.5223/pghn.2015.18.2.121
  35. Favre E, Lion-François L, Canton M, Vanlemmens C, Bonneton M, Bouillet L, Brunet AS, Lachaux A. Cognitive abilities of children with neurological and liver forms of Wilson disease. Journal of Pediatric Gastroenterology and Nutrition. 2017;64(3):436-439.  https://doi.org/10.1097/MPG.0000000000001346
  36. Członkowska A, Litwin T, Chabik G. Wilson disease: neurologic features. Handbook of Clinical Neurology. 2017;142:101-119.  https://doi.org/10.1016/B978-0-444-63625-6.00010-0
  37. Akil M, Brewer GJ. Psychiatric and behavioral abnormalities in Wilson’s disease. Advances in Neurology. 1995;65:171-178. 
  38. Litwin T, Dusek P, Szafrański T, Dzieżyc K, Członkowska A, Rybakowski JK. Psychiatric manifestations in Wilson’s disease: possibilities and difficulties for treatment. Therapeutic Advances in Psychopharmacology. 2018;8(7):199-211.  https://doi.org/10.1177/2045125318759461
  39. Zimbrean PC, Schilsky ML. Psychiatric aspects of Wilson disease: a review. General Hospital Psychiatry. 2014;36(1):53-62.  https://doi.org/10.1016/j.genhosppsych.2013.08.007
  40. Kim TJ, Kim IO, Kim WS, Cheon JE, Moon SG, Kwon JW, Seo JK, Yeon KM. MR imaging of the brain in Wilson disease of childhood: findings before and after treatment with clinical correlation. American Journal of Neuroradiology. 2006;27(6):1373-1378.
  41. Sener RN. The claustrum on MRI: normal anatomy, and the bright claustrum as a new sign in Wilson’s disease. Pediatric Radiology. 1993;23(8):594-596.  https://doi.org/10.1007/BF02014975
  42. Sener RN. Wilson’s disease: MRI demonstration of cavitations in basal ganglia and thalami. Pediatric Radiology. 1993;23(2):157.  https://doi.org/10.1007/BF02012417
  43. Aisen AM, Martel W, Gabrielsen TO, Glazer GM, Brewer G, Young AB, Hill G. Wilson disease of the brain: MR imaging. Radiology. 1985;157(1):137-141.  https://doi.org/10.1148/radiology.157.1.4034959
  44. Nazer H, Brismar J, al-Kawi MZ, Gunasekaran TS, Jorulf KH. Magnetic resonance imaging of the brain in Wilson’s disease. Neuroradiology. 1993;35(2):130-133.  https://doi.org/10.1007/BF00593969
  45. 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(2):531-536.  https://doi.org/10.1148/radiology.198.2.8596862
  46. Zhong W, Huang Z, Tang X. A study of brain MRI characteristics and clinical features in 76 cases of Wilson’s disease. Journal of Clinical Neuroscience. 2019;59:167-174.  https://doi.org/10.1016/j.jocn.2018.10.096
  47. Alkhalik Basha MA, Refaat R, Ahmed AF, Yousef HY, Alsowey AM, Metwally MI, Aly SA, Hussien HM, El-Saadany HF, AlGhobashy AA, Talat MA, Amer MM, Eid AM. Brain magnetic resonance spectroscopy (MRS) as a diagnostic tool for detecting early neurological changes in children with Wilson’s disease. European Journal of Radiology. 2019;111:41-46.  https://doi.org/10.1016/j.ejrad.2018.12.013
  48. Kelly J, Raizman JE, Bevilacqua V, Chan MK, Chen Y, Quinn F, Shodin B, Armbruster D, Adeli K. Complex reference value distributions and partitioned reference intervals across the pediatric age range for 14 specialized biochemical markers in the CALIPER cohort of healthy community children and adolescents. Clinica Chimica Acta. 2015;450:196-202.  https://doi.org/10.1016/j.cca.2015.08.020
  49. Sintusek P, Kyrana E, Dhawan A. Chapter 11. Diagnosis of Hepatic Wilson Disease. In: Weiss KH, Schilsky M, eds. Wilson Disease. Academic Press; 2019:125-138.  https://doi.org/10.1016/B978-0-12-811077-5.00011-6
  50. Gromadzka G, Schmidt HH, Genschel J, Bochow B, Rodo M, Tarnacka B, Litwin T, Chabik G, Członkowska A. Frameshift and nonsense mutations in the gene for ATPase7B are associated with severe impairment of copper metabolism and with an early clinical manifestation of Wilson’s disease. Clinical Genetics. 2005;68(6):524-532.  https://doi.org/10.1111/j.1399-0004.2005.00528.x
  51. Merle U, Eisenbach C, Weiss KH, Tuma S, Stremmel W. Serum ceruloplasmin oxidase activity is a sensitive and highly specific diagnostic marker for Wilson’s disease. Journal of Hepatology. 2009;51(5):925-930. https://doi.org/10.1016/j.jhep.2009.06.022
  52. Costa LS, Pegler SP, Lellis RF, Krebs VL, Robertson S, Morgan T, Honjo RS, Bertola DR, Kim CA. Menkes disease: importance of diagnosis with molecular analysis in the neonatal period. Revista da Associacao Medica Brasileira (1992). 2015;61(5):407-410.  https://doi.org/10.1590/1806-9282.61.05.407
  53. Gitlin JD. Aceruloplasminemia. Pediatric Research. 1998;44(3): 271-276.  https://doi.org/10.1203/00006450-199809000-00001
  54. Mandato C, Brive L, Miura Y, Davis JA, Di Cosmo N, Lucariello S, Pagliardini S, Seo NS, Parenti G, Vecchione R, Freeze HH, Vajro P. Cryptogenic liver disease in four children: a novel congenital disorder of glycosylation. Pediatric Research. 2006;59(2): 293-298.  https://doi.org/10.1203/01.pdr.0000196378.30165.26
  55. Roberts EA, Cox DW. Wilson disease. In: Boyer TD, Manns MP, Sanyal AJ, eds. Zakim and Boyer’s Hepatology. 6th ed. Saint Louis: W.B. Saunders; 2012:1110-1126. https://doi.org/10.1016/B978-1-4377-0881-3.00063-2
  56. Ryan A, Nevitt SJ, Tuohy O, Cook P. Biomarkers for diagnosis of Wilson’s disease. Cochrane Database of Systematic Reviews. 2019;2019(11):CD012267. https://doi.org/10.1002/14651858.CD012267.pub2
  57. Müller T, Koppikar S, Taylor RM, Carragher F, Schlenck B, Heinz-Erian P, Kronenberg F, Ferenci P, Tanner S, Siebert U, Staudinger R, Mieli-Vergani G, Dhawan A. Re-evaluation of the penicillamine challenge test in the diagnosis of Wilson’s disease in children. Journal of Hepatology. 2007;47(2):270-276.  https://doi.org/10.1016/j.jhep.2007.03.011
  58. Palumbo CS, Schilsky ML. Clinical practice guidelines in Wilson disease. Annals of Translational Medicine. 2019;7(Suppl 2):S65.  https://doi.org/10.21037/atm.2018.12.53
  59. Schilsky ML, Roberts EA, Bronstein JM, Dhawan A, Hamilton JP, Rivard AM, Washington MK, Weiss KH, Zimbrean PC. A multidisciplinary approach to the diagnosis and management of Wilson disease: executive summary of the 2022 practice guidance on Wilson disease from the American Association for the Study of Liver Diseases. Hepatology. 2023;77(4):1428-1455. https://doi.org/10.1002/hep.32805
  60. Duncan A, Yacoubian C, Beetham R, Catchpole A, Bullock D. The role of calculated non-caeruloplasmin-bound copper in Wilson’s disease. Annals of Clinical Biochemistry. 2017;54(6):649-654.  https://doi.org/10.1177/0004563216676843
  61. El Balkhi S, Poupon J, Trocello JM, Leyendecker A, Massicot F, Galliot-Guilley M, Woimant F. Determination of ultrafiltrable and exchangeable copper in plasma: stability and reference values in healthy subjects. Analytical and Bioanalytical Chemistry. 2009;394(5):1477-1484. https://doi.org/10.1007/s00216-009-2809-6
  62. El Balkhi S, Trocello JM, Poupon J, Chappuis P, Massicot F, Girardot-Tinant N, Woimant F. Relative exchangeable copper: a new highly sensitive and highly specific biomarker for Wilson’s disease diagnosis. Clinica Chimica Acta. 2011;412(23-24):2254-2260. https://doi.org/10.1016/j.cca.2011.08.019
  63. Guillaud O, Brunet AS, Mallet I, Dumortier J, Pelosse M, Heissat S, Rivet C, Lachaux A, Bost M. Relative exchangeable copper: a valuable tool for the diagnosis of Wilson disease. Liver International. 2018;38(2):350-357.  https://doi.org/10.1111/liv.13520
  64. Poujois A, Trocello JM, Djebrani-Oussedik N, Poupon J, Collet C, Girardot-Tinant N, Sobesky R, Habès D, Debray D, Vanlemmens C, Fluchère F, Ory-Magne F, Labreuche J, Preda C, Woimant F. Exchangeable copper: a reflection of the neurological severity in Wilson’s disease. European Journal of Neurology. 2017;24(1):154-160.  https://doi.org/10.1111/ene.13171
  65. Trocello JM, El Balkhi S, Woimant F, Girardot-Tinant N, Chappuis P, Lloyd C, Poupon J. Relative exchangeable copper: a promising tool for family screening in Wilson disease. Movement Disorders. 2014;29(4):558-562.  https://doi.org/10.1002/mds.25763
  66. Yim J, Kwon SB, Han JS, Kim JH, Lee EH, Lee SG. Total and exchangeable copper assay using inductively coupled plasma mass spectrometry and establishment of a pediatric reference interval. Archives of Pathology and Laboratory Medicine. 2021;145(7):877-882.  https://doi.org/10.5858/arpa.2020-0029-OA
  67. Ferenci P, Ott P. Wilson’s disease: fatal when overlooked, curable when diagnosed. Journal of Hepatology. 2019;71(1):222-224.  https://doi.org/10.1016/j.jhep.2019.02.002
  68. Beinhardt S, Leiss W, Stättermayer AF, Graziadei I, Zoller H, Stauber R, Maieron A, Datz C, Steindl-Munda P, Hofer H, Vogel W, Trauner M, Ferenci P. Long-term outcomes of patients with Wilson disease in a large Austrian cohort. Clinical Gastroenterology and Hepatology. 2014;12(4):683-689.  https://doi.org/10.1016/j.cgh.2013.09.025
  69. Seo JK. Diagnosis of Wilson disease in young children: Molecular genetic testing and a paradigm shift from the laboratory diagnosis. Pediatric Gastroenterology, Hepatology and Nutrition. 2012;15(4):197-209.  https://doi.org/10.5223/pghn.2012.15.4.197
  70. Espinós C, Ferenci P. Are the new genetic tools for diagnosis of Wilson disease helpful in clinical practice? JHEP Reports. 2020; 2(4):100114. https://doi.org/10.1016/j.jhepr.2020.100114
  71. Ferenci P, Stremmel W, Członkowska A, Szalay F, Viveiros A, Stättermayer AF, Bruha R, Houwen R, Pop TL, Stauber R, Gschwantler M, Pfeiffenberger J, Yurdaydin C, Aigner E, Steindl-Munda P, Dienes HP, Zoller H, Weiss KH. Age and sex but Not ATP7B genotype effectively influence the clinical phenotype of Wilson disease. Hepatology. 2019;69(4):1464-1476. https://doi.org/10.1002/hep.30280
  72. Mukherjee S, Dutta S, Majumdar S, Biswas T, Jaiswal P, Sengupta M, Bhattacharya A, Gangopadhyay PK, Bavdekar A, Das SK, Ray K. Genetic defects in Indian Wilson disease patients and genotype phenotype correlation. Parkinsonism&Related Disorders. 2014; 20(1):75-81.  https://doi.org/10.1016/j.parkreldis.2013.09.021
  73. Collins CJ, Yi F, Dayuha R, Duong P, Horslen S, Camarata M, Coskun AK, Houwen RHJ, Pop TL, Zoller H, Yoo HW, Jung SW, Weiss KH, Schilsky ML, Ferenci P, Hahn SH. Direct measurement of ATP7B peptides is highly effective in the diagnosis of Wilson disease. Gastroenterology. 2021;160(7):2367-2382.e1.  https://doi.org/10.1053/j.gastro.2021.02.052
  74. Mayr T, Ferenci P, Weiler M, Fichtner A, Mehrabi A, Hoffmann GF, Mohr I, Pfeiffenberger J, Weiss KH, Teufel-Schäfer U. Optimized Trientine-dihydrochloride Therapy in Pediatric Patients With Wilson Disease: Is Weight-based Dosing Justified? Journal of Pediatric Gastroenterology and Nutrition. 2021;72(1):115-122.  https://doi.org/10.1097/MPG.0000000000002902
  75. Scheinberg IH, Jaffe ME, Sternlieb I. The use of trientine in preventing the effects of interrupting penicillamine therapy in Wilson’s disease. New England Journal of Medicine. 1987;317(4):209-213.  https://doi.org/10.1056/NEJM198707233170405
  76. Walshe JM. Treatment of Wilson’s disease with trientine (triethylene tetramine) dihydrochloride. Lancet. 1982;1(8273):643-647.  https://doi.org/10.1016/S0140-6736(82)92201-2
  77. Dubois RS, Rodgerson DO, Hambidge KM. Treatment of Wilson’s disease with triethylene tetramine hydrochloride (Trientine). Journal of Pediatric Gastroenterology and Nutrition. 1990;10(1):77-81.  https://doi.org/10.1097/00005176-199001000-00015
  78. Merle U, Schaefer M, Ferenci P, Stremmel W. Clinical presentation, diagnosis and long-term outcome of Wilson’s disease: a cohort study. Gut. 2007;56(1):115-120.  https://doi.org/10.1136/gut.2005.087262
  79. Weiss KH, Thurik F, Gotthardt DN, Schäfer M, Teufel U, Wiegand F, Merle U, Ferenci-Foerster D, Maieron A, Stauber R, Zoller H, Schmidt HH, Reuner U, Hefter H, Trocello JM, Houwen RH, Ferenci P, Stremmel W; EUROWILSON Consortium. Efficacy and safety of oral chelators in treatment of patients with Wilson disease. Clinical Gastroenterology and Hepatology. 2013; 11(8):1028-1035.e1-2.  https://doi.org/10.1016/j.cgh.2013.03.012
  80. Sturm E, Piersma FE, Tanner MS, Socha P, Roberts EA, Shneider BL. Controversies and variation in diagnosing and treating children with Wilson disease: results of an international survey. Journal of Pediatric Gastroenterology and Nutrition. 2016;63(1):82-87.  https://doi.org/10.1097/MPG.0000000000001102
  81. Aggarwal A, Bhatt M. Advances in treatment of Wilson Disease. Tremor and Other Hyperkinetic Movements (New York, N.Y.). 2018;8:525.  https://doi.org/10.5334/tohm.435
  82. Scheinberg IH, Sternlieb I, Schilsky M, Stockert RJ. Penicillamine may detoxify copper in Wilson’s disease. Lancet. 1987;2(8550):95.  https://doi.org/10.1016/S0140-6736(87)92753-X
  83. Litwin T, Dzieżyc K, Karliński M, Chabik G, Czepiel W, Członkowska A. Early neurological worsening in patients with Wilson’s disease. Journal of the Neurological Sciences. 2015;355(1-2):162-167.  https://doi.org/10.1016/j.jns.2015.06.010
  84. Brewer GJ. Zinc acetate for the treatment of Wilson’s disease. Expert Opinion on Pharmacotherapy. 2001;2(9):1473-1477. https://doi.org/10.1517/14656566.2.9.1473
  85. Schilsky ML, Blank RR, Czaja MJ, Zern MA, Scheinberg IH, Stockert RJ, Sternlieb I. Hepatocellular copper toxicity and its attenuation by zinc. Journal of Clinical Investigation. 1989;84(5): 1562-1568. https://doi.org/10.1172/JCI114333
  86. Alvarez HM, Xue Y, Robinson CD, Canalizo-Hernández MA, Marvin RG, Kelly RA, Mondragón A, Penner-Hahn JE, O’Halloran TV. Tetrathiomolybdate inhibits copper trafficking proteins through metal cluster formation. Science. 2010;327(5963):331-334.  https://doi.org/10.1126/science.1179907
  87. Brewer GJ, Askari F, Lorincz MT, Carlson M, Schilsky M, Kluin KJ, Hedera P, Moretti P, Fink JK, Tankanow R, Dick RB, Sitterly J. 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. Archives of Neurology. 2006;63(4):521-527.  https://doi.org/10.1001/archneur.63.4.521
  88. Pöhler M, Guttmann S, Nadzemova O, Lenders M, Brand E, Zibert A, Schmidt HH, Sandfort V. CRISPR/Cas9-mediated correction of mutated copper transporter ATP7B. PLoS One. 2020; 15(9):e0239411. https://doi.org/10.1371/journal.pone.0239411
  89. Santos Silva EE, Sarles J, Buts JP, Sokal EM. Successful medical treatment of severely decompensated Wilson disease. Journal of Pediatrics. 1996;128(2):285-287.  https://doi.org/10.1016/S0022-3476(96)70412-2
  90. 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 Transplantation. 2005;11(4):441-448.  https://doi.org/10.1002/lt.20352
  91. Koppikar S, Dhawan A. Evaluation of the scoring system for the diagnosis of Wilson’s disease in children. Liver International. 2005; 25(3):680-681.  https://doi.org/10.1111/j.1478-3231.2005.01072.x
  92. Filippi C, Dhawan A. Current status of human hepatocyte transplantation and its potential for Wilson’s disease. Annals of the New York Academy of Sciences. 2014;1315:50-55.  https://doi.org/10.1111/nyas.12386
  93. Iansante V, Mitry RR, Filippi C, Fitzpatrick E, Dhawan A. Human hepatocyte transplantation for liver disease: Current status and future perspectives. Pediatric Research. 2018;83(1-2):232-240.  https://doi.org/10.1038/pr.2017.284
  94. Greig JA, Nordin JML, Smith MK, Ashley SN, Draper C, Zhu Y, Bell P, Buza EL, Wilson JM. A gene therapy approach to improve copper metabolism and prevent liver damage in a mouse model of Wilson disease. Human Gene Therapy. Clinical Development. 2019;30(1):29-39.  https://doi.org/10.1089/humc.2018.219
  95. Meng Y, Miyoshi I, Hirabayashi M, Su M, Mototani Y, Okamura T, Terada K, Ueda M, Enomoto K, Sugiyama T, Kasai N. Restoration of copper metabolism and rescue of hepatic abnormalities in LEC rats, an animal model of Wilson disease, by expression of human ATP7B gene. Biochimica et Biophysica Acta. 2004;1690(3):208-219.  https://doi.org/10.1016/j.bbadis.2004.06.022
  96. Merle U, Stremmel W, Encke J. Perspectives for gene therapy of Wilson disease. Current Gene Therapy. 2007;7(3):217-220.  https://doi.org/10.2174/156652307780859053
  97. Roy-Chowdhury J, Schilsky ML. Gene therapy of Wilson disease: A “golden” opportunity using rAAV on the 50th anniversary of the discovery of the virus. Journal of Hepatology. 2016;64(2): 265-267.  https://doi.org/10.1016/j.jhep.2015.11.017
  98. Chanpong A, Dhawan A. Long term urinary copper excretion on Chelation therapy in children with Wilson disease. Journal of Pediatric Gastroenterology and Nutrition. 2021;72(2):210-215.  https://doi.org/10.1097/MPG.0000000000002982
  99. Espinós C, Ferenci P. Are the new genetic tools for diagnosis of Wilson disease helpful in clinical practice? JHEP reports. 2020; 2(4):100114. https://doi.org/10.1016/j.jhepr.2020.100114
  100. Dudani K, Solanki RK, Sharma P, Singh D. Adolescent onset Wilson’s disease misdiagnosed as psychosis. Indian Journal of Psychiatry. 2016;58(4):480-481.  https://doi.org/10.4103/0019-5545.196716
  101. Azova S, Rice T, Garcia-Delgar B, Coffey BJ. New-onset psychosis in an adolescent with Wilson’s disease. Journal of Child and Adolescent Psychopharmacology. 2016;26(3):301-304.  https://doi.org/10.1089/cap.2016.29106.bjc
  102. Masełbas W, Chabik G, Członkowska A. Persistence with treatment in patients with Wilson disease. Neurologia i Neurochirurgia Polska. 2010;44(3):260-263.  https://doi.org/10.1016/S0028-3843(14)60040-2
  103. Walshe JM, Waldenström E, Sams V, Nordlinder H, Westermark K. Abdominal malignancies in patients with Wilson’s disease. QJM. 2003;96(9):657-562.  https://doi.org/10.1093/qjmed/hcg114
  104. Kaushansky A, Frydman M, Kaufman H, Homburg R. Endocrine studies of the ovulatory disturbances in Wilson’s disease (hepatolenticular degeneration). Fertility and Sterility. 1987; 47(2):270-273.  https://doi.org/10.1016/S0015-0282(16)50004-1
  105. Pfeiffenberger J, Beinhardt S, Gotthardt DN, Haag N, Freissmuth C, Reuner U, Gauss A, Stremmel W, Schilsky ML, Ferenci P, Weiss KH. Pregnancy in Wilson’s disease: Management and outcome. Hepatology. 2018;67(4):1261-1269. https://doi.org/10.1002/hep.29490
  106. Malik A, Khawaja A, Sheikh L. Wilson’s disease in pregnancy: Case series and review of literature. BMC Research Notes. 2013;6:421.  https://doi.org/10.1186/1756-0500-6-421
Contact the author
Email
Message
The publishing house "Media Sphere" does not provide treatment services, does not give recommendations on contacting medical institutions and specific specialists, on the prescription of medicines and dietary supplements.

Email Confirmation

An email was sent to test@gmail.com with a confirmation link. Follow the link from the letter to complete the registration on the site.

Email Confirmation

Contact us
If you have any questions, complaints or suggestions, please use this feedback form.
Email
Message
The publishing house "Media Sphere" does not provide treatment services, does not give recommendations on contacting medical institutions and specific specialists, on the prescription of medicines and dietary supplements.
Submit Application

You can become an author of one of our magazines, send a request and we will consider it in during the day.

Name
Phone
E-mail
Message
Login
Registration
E-mail
Password
Forgot Password?

Log in to the site using your account in one of the services

Password recovery
E-mail
Login
Register

We use cооkies to improve the performance of the site. By staying on our site, you agree to the terms of use of cооkies. To view our Privacy and Cookie Policy, please. click here.