GENETIC DIAGNOSTICS AND CLINICAL FEATURES OF WILSON’S DISEASE IN CHILDREN
Abstract
A disorder of copper metabolism at Wilson’s disease (WD), conditioned by a mutation of adenosine thriphospate P-type gene (ATP7B), results in irreversible changes in the liver and in the nervous system. Mortality is high at WD, but it is one of hereditary diseases, well subjected to the therapy. The disease is manifested in the early age, but its clinical course in children is symptomless that essentially complicates diagnostics. A single reliable method is genetic analysis for revealing mutations in ATP7B gene.
The aim of the work was to analyze clinical manifestations and course of Wilson’s disease cases, genetically verified in children by detecting mutations of ATP7B gene.
The research group included children of 6-17 years old with different injury degrees of the hepatobiliary system. According to results of the molecular-genetic analysis, the most spread allele variant of ATP7B gene (H1069Q) in Europe was confirmed in 10 patients of child age, including 4 cases of homozygosity.
In 10 cases of the confirmed diagnosis of Wilson’s disease in child age in 100% (in all 10) of persons, a clinical manifestation was characterized by disorders from the hepatobiliary system, and only in 1 (10 %) – changes from the nervous system. At raising the level of transaminase in children, even at the normal bilirubin level and negative tests for viral hepatitis, it is recommended to carry out genetic testing for Wilson’s diseaseKeywords
Full Text:
PDFReferences
Roberts, E. A., Socha, P. (2017). Wilson disease in children. Handbook of Clinical Neurology, 141–156. doi: https://doi.org/10.1016/b978-0-444-63625-6.00012-4
Gao, J., Brackley, S., Mann, J. P. (2018). The global prevalence of Wilson disease from next-generation sequencing data. Genetics in Medicine, 21 (5), 1155–1163. doi: https://doi.org/10.1038/s41436-018-0309-9
Yuan, Z.-F., Wu, W., Yu, Y.-L., Shen, J., Mao, S.-S., Gao, F., Xia, Z.-Z. (2015). Novel mutations of the ATP7B gene in Han Chinese families with pre-symptomatic Wilson’s disease. World Journal of Pediatrics, 11 (3), 255–260. doi: https://doi.org/10.1007/s12519-015-0031-5
Socha, P., Janczyk, W., Dhawan, A., Baumann, U., D’Antiga, L., Tanner, S. et. al. (2018). Wilsonʼs Disease in Children. Journal of Pediatric Gastroenterology and Nutrition, 66 (2), 334–344. doi: https://doi.org/10.1097/mpg.0000000000001787
Trufanov, Y. O. (2018). Diagnosis and treatment: wilson’s disease. World of Medicine and Biology, 4 (66), 117–120. doi: https://doi.org/10.26724/2079-8334-2018-4-66-117-120
Trufanov, Ye. A., Penner, V. A., Mishchenko, M. V., Lomova, I. V. (2012). Klinicheskiy sluchay bolezni Konovalova-Vilsona: trudnosti diagnostiki. Ukrayinskyi medychnyi almanakh, 15 (5), 460–462.
Seo, J. K. (2012). Diagnosis of Wilson Disease in Young Children: Molecular Genetic Testing and a Paradigm Shift from the Laboratory Diagnosis. Pediatric Gastroenterology, Hepatology & Nutrition, 15 (4), 197. doi: https://doi.org/10.5223/pghn.2012.15.4.197
Li, H., Liu, L., Li, Y., He, S., Liu, Y., Li, J. et. al. (2018). Familial screening of children with Wilson disease. Medicine, 97 (27), e11405. doi: https://doi.org/10.1097/md.0000000000011405
Ministerstvo okhorony zdorovia Ukrainy. Nakaz vid 26 lypnia 2016 roku No. 769. Unifikovanyi klinichnyi protokol pervynnoi ta vtorynnoi (spetsializovanoi) medychnoi dopomohy. Khvoroba Vilsona.
Ferenci, P., Caca, K., Loudianos, G., Mieli-Vergani, G., Tanner, S., Sternlieb, I. et. al. (2003). Diagnosis and phenotypic classification of Wilson disease1. Liver International, 23 (3), 139–142. doi: https://doi.org/10.1034/j.1600-0676.2003.00824.x
Brunet, A.-S., Marotte, S., Guillaud, O., Lachaux, A. (2012). Familial screening in Wilson’s disease: Think at the previous generation! Journal of Hepatology, 57 (6), 1394–1395. doi: https://doi.org/10.1016/j.jhep.2012.07.011
Roberts, E. A., Schilsky, M. L. (2008). Diagnosis and treatment of Wilson disease: An update. Hepatology, 47 (6), 2089–2111. doi: https://doi.org/10.1002/hep.22261
Patil, M., Sheth, K. A., Krishnamurthy, A. C., Devarbhavi, H. (2013). A Review and Current Perspective on Wilson Disease. Journal of Clinical and Experimental Hepatology, 3 (4), 321–336. doi: https://doi.org/10.1016/j.jceh.2013.06.002
Alam, S. T., Rahman, M. M., Islam, K. A. et. al. (2014). Neurologic manifestations, diagnosis and management of Wilson's disease in children: an update. Mymensingh Med. J., 23, 195–203.
Hedera, P. (2017). Update on the clinical management of Wilson’s disease. The Application of Clinical Genetics, 10, 9–19. doi: https://doi.org/10.2147/tacg.s79121
Liu, J., Luan, J., Zhou, X., Cui, Y., Han, J. (2017). Epidemiology, diagnosis, and treatment of Wilson's disease. Intractable & Rare Diseases Research, 6 (4), 249–255. doi: https://doi.org/10.5582/irdr.2017.01057
Ponomarev, V. V. (2010). Bolezn Konovalova-Vilsona: “velikiy khameleon”. Mezhdunarodnyi nevrologicheskiy zhurnal, 3 (33), 117–122.
Rodriguez-Castro, K. I. (2015). Wilson’s disease: A review of what we have learned. World Journal of Hepatology, 7 (29), 2859. doi: https://doi.org/10.4254/wjh.v7.i29.2859
Aggarwal, A., Bhatt, M. (2013). Update on Wilson Disease. Metal Related Neurodegenerative Disease, 313–348. doi: https://doi.org/10.1016/b978-0-12-410502-7.00014-4
De Bem, R. S., Raskin, S., Muzzillo, D. A., Deguti, M. M., Cancado, E. L. R., Araujo, T. F., Nakhle, M. C. et. al. (2013). Wilson's disease in Southern Brazil: genotype-phenotype correlation and description of two novel mutations in ATP7B gene. Arquivos de Neuro-Psiquiatria, 71 (8), 503–507. doi: https://doi.org/10.1590/0004-282x20130078
Deguti, M. M., Genschel, J., Cancado, E. L. R., Barbosa, E. R., Bochow, B., Mucenic, M. et. al. (2004). Wilson disease: Novel mutations in theATP7B gene and clinical correlation in Brazilian patients. Human Mutation, 23 (4), 398–398. doi: https://doi.org/10.1002/humu.9227
EASL Clinical Practice Guidelines: Wilson’s disease (2012). Journal of Hepatology, 56 (3), 671–685. doi: https://doi.org/10.1016/j.jhep.2011.11.007
Haiboniuk, I. (2019). Spectrum and frequency of ATP7B gene mutations in various populations and ethnic groups. Visnyk of Lviv University. Biological Series, 80, 3–11. doi: https://doi.org/10.30970/vlubs.2019.80.01
Haiboniuk, I., Makukh, H., Tyrkus, M., Tretiak, B., Jadzhyn, L. (2019). Mutations H1069Q of ATP7B gene and C282Y and H63D of HFE gene in persons with hepatobilary diseases of undefined genesis. Bulletin of Problems Biology and Medicine, 1 (2), 224. doi: https://doi.org/10.29254/2077-4214-2019-1-2-149-224-229
Li, H., Liu, L., Li, Y., He, S., Liu, Y., Li, J. et. al. (2018). Familial screening of children with Wilson disease. Medicine, 97 (27), e11405. doi: https://doi.org/10.1097/md.0000000000011405
Makukh, H. V., Zastavna, D. V., Tyrkus, M. Y., Tretiak, B. I., Chorna, L. B. (2008). Pat. No. 32044 UA. Method for separation of DNA from leucocytes of peripheral blood. No. u200801896; declareted: 14.02.2008; published: 25.04.2008, Bul. No. 8.
Wilson’s Disease Scoring System. Available at: https://gastroliver.medicine.ufl.edu/hepatology/for-physicians/wilsons-disease-scoring-system/
Polakova, H., Katrincsakova, B., Minarik, G., Ferakova, E., Ficek, A., Baldovic, M., Kádasi, L. (2007). Detection of His1069Gln mutation in Wilson disease by bidirectional PCR amplification of specific alleles (BI-PASA) test. Gen. Physiol. Biophys, 26 (2), 91–96.
DOI: http://dx.doi.org/10.21303/2504-5695.2020.001197
Refbacks
- There are currently no refbacks.
Copyright (c) 2020 Ivanna Haiboniuk, Marta Dats-Opoka, Halyna Makukh, Yaryna Boyko, Igor Kiselyk

This work is licensed under a Creative Commons Attribution 4.0 International License.
ISSN 2504-5695 (Online), ISSN 2504-5687 (Print)