Abstract
Objective: Wilson’s disease is an autosomal recessive disorder characterized by copper metabolism disorder. Prognosis depends on the severity of liver involvement and neurological findings. Neurological involvement can sometimes be the first symptom in patients, early diagnosis and treatment can control brain damage and symptoms. In this study, we wanted to emphasize the importance of neurological involvement of the disease.
Material and Methods: This study included Wilson patients with neurological findings who applied to Pediatric Neurology Department between April 2008 and May 2018. The age, gender distribution, complaints of the patients, neurological symptoms, hepatological findings, treatments and treatment responses were analyzed retrospectively. A detailed neurological examination was performed on all 42 Wilson patients who were eligible. Fifteen patients with neurological findings were evaluated.
Results: The mean age of the patients was 12.5±3.6 years (8-20 years), 53.3% male, 46.7% female. Hepatologic symptoms were present in 66.7% of the patients, neurological symptoms in 35.7% and Kayser-Fleischer ring in 26.7% of the patients. The most common symptoms in patients with neurological findings were ataxia and tremor (40%). Other symptoms were dystonia (13.4%), korea (6.6%), seizures (13.4%), behavioral disorders (13.4%), dysarthria and sialorrhea (13.4%). Radiologic findings were present in 10 (66.7%) of the patients with neurological findings. Ten patients received penicilamine treatment and five patients received trientine treatment. At the end of the first year of treatment, neurological symptoms improved in 80% of those receiving trientine treatment and in 50% of those receiving penicillamine treatment.
Conclusion: Neurological involvement is common in Wilson’s disease. Since the findings may be overlooked at the beginning of the disease, neurological examination should be performed in all patients receiving the diagnosis. Wilson’s disease should also be kept in mind in etiology in patients with movement disorder.
Keywords
References
- 1. Huster D. Wilson disease. Best Pract Res Clin Gastroenterol 2010; 24:531-9.
- 2. Dedoussis GV, Genschel J, Sialvera TE, Bochow B, Manolaki N, Manios Y, et al. Wilson disease: high prevalence in a mountainous area of Crete. Ann Hum Genet 2005; 69:268-74.
- 3. Feldstein AE, Chitkara DK, Plescow R, Grand RJ. Wilson Disease In Pediactric Gastrointestinal Disease by Walker WA. 2004 IV.Ed., BC Decker Inc, Ontario, 1440-54.
- 4. Ala A, Schilsky ML. Wilson disease: pathophysiology, diagnosis, treatment, and screening. Clin Liver Dis 2004; 8:787-805.
- 5. Salari M, Fayyazi E, Mirmosayyeb O. Magnetic resonance imaging findings in diagnosis and prognosis of Wilson disease. J Res Med Sci 2018; 27:23-5.
- 6. Machado A, Chien HF, Deguti MM, Cançado E, Azevedo RS, Scaff M. Neurological manifestations in Wilson’s disease: Report of 119 cases. Mov Disord 2006; 21:2192-6.
- 7. Pfeiffer RF. Wilson’s Disease. Semin Neurol 2007; 27:123-32. 8. Ferenci P, Caca K, Loudianos G, Mieli-Vergani G, Tanner S, Sternlieb I. Diagnosis and phenotypic classification of Wilson disease. Liver Int 2003; 23:139-42.
- 9. Roberts EA, Schilsky ML. American Association for Study of Liver Diseases (AASLD). Diagnosis and treatment of Wilson disease: an update. Hepatology 2008; 47:2089-111.
- 10. European Association for Study of Liver. EASL Clinical Practice Guidelines: Wilson’s disease. J Hepatol 2012;56:671-85.
- 11. 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; 36:157-65.
- 12. Litwin T, Gromadzka G, Członkowska A. Gender differences in Wilson’s disease. J Neurol Sci 2012; 312:31-5.
- 13. Bie P, Muller P, Wijmenga C, Klomp JWL. Molecular pathogenesis of Wilson and Menkes disease: correlation of mutations with molecular defects and disease phenotypes. J Med Genet 2017; 44:673-88.
- 14. Ferenci P. Pathophysiology and clinical features of Wilson disease. Metab Brain Dis 2004; 19:229-39.
- 15. Steindl P, Ferenci P, Dienes HP, Grimm G, Pabinger I, Madl C et al. Wilson’s disease in patients presenting with liver disease: a diagnostic challenge. Gastroenterology 1997; 113:212-8.
- 16. Rukunuzzaman M. Wilson’s disease in Bangladeshi children: analysis of 100 cases. Pediatr Gastroenterol Hepatol Nutr 2015;18:121-7.
- 17. Deguti M, Tietge UJF, Barbosa ER. The eye in Wilson’s disease: sunflower cataract associated with Kaiser–Fleischer ring. J Hepatol 2002; 37:700.
- 18. Fenu M, Liggi M, Demelia E, Sorbello O, Civolani A, Demelia L. Kayser–Fleischer ring in Wilson’s disease: A cohort study. Eur J Intern Med 2012;23:150-6.
- 19. Youn J, Kim J, Kim H, Lee J, Lee P, Ki C, et al. Characteristics of neurological Wilson’s disease without Kayser-Fleischer ring. J Neurol Sci 2012; 323:183-6.
- 20. Bayram AK, Gümüş H, Arslan D, Özcora GK, Kumandaş S, Karacabey N ve et al. Neurological features and management of Wilson disease in children: An evaluation of 12 cases. Turk Pediatri Ars 2016;51:15-21.
- 21. Lorincz MT. Neurologic Wilson’s disease. Ann N Y Acad Sci 2010; 1184:173-87.
- 22. Czlonkowska A, Litwin T, Dziezyc K, Karliński M, Bring J, Bjartmar C. Characteristics of a newly diagnosed Polish chort of patients with neurological manifestations of Wilson disease evaluated with the Unified Wilson’s Disease Rating Scale. BMC Neurology 2018;18:34.
- 23. Osborn AG, Blaser SI, Salzman KL, Katzman GL, Provenzale J, Castillo M, et al. Metabolic/Degenerative Disorders, Inherited In Diagnostic Imaging Brain. Utah: 203. Amirsys 2004: 72-75.
- 24. Andersen K, Sudmeyer M, Saleh A. Cerebral imaging for Wilson disease. Rofo 2007:179:225-33.
- 25. Dening TR, Berrios GE, Walshe JM. Wilson’s disease and epilepsy. Brain 1988; 111:1139-55.
- 26. Seniów J, Bak T, Gajda J, Poniatowska R, Czlonkowska A. Cognitive functioning in neurologically symptomatic and asymptomatic forms of Wilson’s disease. Mov Disord 2002; 17:1077-83.
- 27. Hanağası F, Hanağası H. Wilson Hastalığı. Turk J Neurol 2013;19:122-7.
- 28. Schilsky ML. Treatment of Wilson’s disease: What are the relative roles of penicillamine, trientine, and zinc supplementation? Curr Gastroenterol Rep 2001; 3:54-9.
- 29. Pall HS, Williams AC, Blake DR. Deterioration of Wilson’s disease following the start of penicillamine therapy. Arch Neurol 1989; 46: 359-60.
- 30. Brewer GJ, Hedera P, Kluin KJ, Carlson M, Ascari F, Dick RB, et al. Treatment of Wilson disease with ammonium tetrathiomolybdate: III. Initial therapy in a total of 55 neurologically affected patients and follow-up with zinc therapy. Arch Neurol 2003; 60: 379-85.
- 31. Iorio R, D’Ambrosi M, Marcellini M, Barbera C, Maggiore G, Zancan L, et al. Serum transaminases in children with Wilson’s disease. J Pediatr Gastroenterol Nutr 2004; 39: 331-6.
- 32. Wiggelinkhuizen M, Tilanus ME, Bollen CW, Houwen RH. Systematic review: clinical efficacy of chelator agents and zinc in the initial treatment of Wilson disease. Aliment Pharmacol Ther 2009; 29: 947-58.
- 33. Burke JF, Dayalu P, Nan B, Askari F, Brewer GJ, Lorincz MT. Prognostic significance of neurologic examination findings in Wilson disease. Park Rel Disord 2011;17:551-6.
- 34. Hefter H, Tezayak O. Rosenthal D. Long-term outcome of neurological Wilson ́s disease. Parkinsonism Relat Disord 2018;49:48-53
Abstract
Amaç: Wilson hastalığı otozomal resesif geçiş gösteren, bakır metabolizma bozukluğu ile karakterize bir hastalıktır. Prognoz hastalığın karaciğer tutulumunun şiddetine ve nörolojik bulgulara bağlıdır. Nörolojik tutulum hastalarda bazen ilk bulgu olabilir, erken tanı ve tedavi beyin hasarı ve semptomları kontrol edebilir. Biz bu çalışmada hastalığın nörolojik tutulumun önemini vurgulamak istedik.
Gereç ve Yöntemler: Bu çalışmaya Nisan 2008 ile Mayıs 2018 tarihleri arasında Çocuk Nöroloji Bilim Dalı Polikliniğine başvuran nörolojik bulguları olan Wilson hastaları dahil edildi. Hastaların yaşları, cinsiyet dağılımları, başvuru şikayetleri, nörolojik semptomları, hepatolojik bulguları, tedavileri, tedaviye verdikleri cevap retrospektif olarak incelendi. Takipli olan 42 Wilson tanısı alan hastaların hepsine ayrıntılı nörolojik muayene yapıldı. Nörolojik bulgusu olan 15 hasta değerlendirildi.
Bulgular: Hastaların yaş ortalaması 12.5±3.6yaş (8-20 yaş), %53.3’ü erkek, %46.7’si kızdı. Hastaların %66.7’sinde hepatolojik semptomlar, %35.7’sinde nörolojik semptomlar ve %26.7’sinde Kayser-Fleischer halkası mevcuttu. Nörolojik bulguları olan hastalarda en sık karşılaşılan semptomlar ataksi ve tremordu (%40). Diğer semptomlar distoni (%13.4), kore (%6.6), nöbet (%13.4), davranış bozukluğu (%13.4), dizartri ve sialore (%13.4)’dı. Nörolojik bulgusu olanların 10’unda (%66.7) radyolojik bulgular vardı. On hastaya penisilamin, 5 hastaya trientin başlandı. Tedavinin 1. yılının sonunda nörolojik semptomlarda trientin tedavisi alanların %80’inde, penisilamin tedavisi alanların %50’sinde düzelme oldu.
Sonuç: Wilson hastalığında nörolojik tutulum sık görülür. Bulgular hastalığın başlangıcında gözden kaçabileceği için tanı alan tüm hastalarda nörolojik muayene yapılmalıdır. Ayrıca hareket bozukluğu ile başvuran hastalarda etyolojide Wilson hastalığı akılda tutulmalıdır.
Keywords
References
- 1. Huster D. Wilson disease. Best Pract Res Clin Gastroenterol 2010; 24:531-9.
- 2. Dedoussis GV, Genschel J, Sialvera TE, Bochow B, Manolaki N, Manios Y, et al. Wilson disease: high prevalence in a mountainous area of Crete. Ann Hum Genet 2005; 69:268-74.
- 3. Feldstein AE, Chitkara DK, Plescow R, Grand RJ. Wilson Disease In Pediactric Gastrointestinal Disease by Walker WA. 2004 IV.Ed., BC Decker Inc, Ontario, 1440-54.
- 4. Ala A, Schilsky ML. Wilson disease: pathophysiology, diagnosis, treatment, and screening. Clin Liver Dis 2004; 8:787-805.
- 5. Salari M, Fayyazi E, Mirmosayyeb O. Magnetic resonance imaging findings in diagnosis and prognosis of Wilson disease. J Res Med Sci 2018; 27:23-5.
- 6. Machado A, Chien HF, Deguti MM, Cançado E, Azevedo RS, Scaff M. Neurological manifestations in Wilson’s disease: Report of 119 cases. Mov Disord 2006; 21:2192-6.
- 7. Pfeiffer RF. Wilson’s Disease. Semin Neurol 2007; 27:123-32. 8. Ferenci P, Caca K, Loudianos G, Mieli-Vergani G, Tanner S, Sternlieb I. Diagnosis and phenotypic classification of Wilson disease. Liver Int 2003; 23:139-42.
- 9. Roberts EA, Schilsky ML. American Association for Study of Liver Diseases (AASLD). Diagnosis and treatment of Wilson disease: an update. Hepatology 2008; 47:2089-111.
- 10. European Association for Study of Liver. EASL Clinical Practice Guidelines: Wilson’s disease. J Hepatol 2012;56:671-85.
- 11. 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; 36:157-65.
- 12. Litwin T, Gromadzka G, Członkowska A. Gender differences in Wilson’s disease. J Neurol Sci 2012; 312:31-5.
- 13. Bie P, Muller P, Wijmenga C, Klomp JWL. Molecular pathogenesis of Wilson and Menkes disease: correlation of mutations with molecular defects and disease phenotypes. J Med Genet 2017; 44:673-88.
- 14. Ferenci P. Pathophysiology and clinical features of Wilson disease. Metab Brain Dis 2004; 19:229-39.
- 15. Steindl P, Ferenci P, Dienes HP, Grimm G, Pabinger I, Madl C et al. Wilson’s disease in patients presenting with liver disease: a diagnostic challenge. Gastroenterology 1997; 113:212-8.
- 16. Rukunuzzaman M. Wilson’s disease in Bangladeshi children: analysis of 100 cases. Pediatr Gastroenterol Hepatol Nutr 2015;18:121-7.
- 17. Deguti M, Tietge UJF, Barbosa ER. The eye in Wilson’s disease: sunflower cataract associated with Kaiser–Fleischer ring. J Hepatol 2002; 37:700.
- 18. Fenu M, Liggi M, Demelia E, Sorbello O, Civolani A, Demelia L. Kayser–Fleischer ring in Wilson’s disease: A cohort study. Eur J Intern Med 2012;23:150-6.
- 19. Youn J, Kim J, Kim H, Lee J, Lee P, Ki C, et al. Characteristics of neurological Wilson’s disease without Kayser-Fleischer ring. J Neurol Sci 2012; 323:183-6.
- 20. Bayram AK, Gümüş H, Arslan D, Özcora GK, Kumandaş S, Karacabey N ve et al. Neurological features and management of Wilson disease in children: An evaluation of 12 cases. Turk Pediatri Ars 2016;51:15-21.
- 21. Lorincz MT. Neurologic Wilson’s disease. Ann N Y Acad Sci 2010; 1184:173-87.
- 22. Czlonkowska A, Litwin T, Dziezyc K, Karliński M, Bring J, Bjartmar C. Characteristics of a newly diagnosed Polish chort of patients with neurological manifestations of Wilson disease evaluated with the Unified Wilson’s Disease Rating Scale. BMC Neurology 2018;18:34.
- 23. Osborn AG, Blaser SI, Salzman KL, Katzman GL, Provenzale J, Castillo M, et al. Metabolic/Degenerative Disorders, Inherited In Diagnostic Imaging Brain. Utah: 203. Amirsys 2004: 72-75.
- 24. Andersen K, Sudmeyer M, Saleh A. Cerebral imaging for Wilson disease. Rofo 2007:179:225-33.
- 25. Dening TR, Berrios GE, Walshe JM. Wilson’s disease and epilepsy. Brain 1988; 111:1139-55.
- 26. Seniów J, Bak T, Gajda J, Poniatowska R, Czlonkowska A. Cognitive functioning in neurologically symptomatic and asymptomatic forms of Wilson’s disease. Mov Disord 2002; 17:1077-83.
- 27. Hanağası F, Hanağası H. Wilson Hastalığı. Turk J Neurol 2013;19:122-7.
- 28. Schilsky ML. Treatment of Wilson’s disease: What are the relative roles of penicillamine, trientine, and zinc supplementation? Curr Gastroenterol Rep 2001; 3:54-9.
- 29. Pall HS, Williams AC, Blake DR. Deterioration of Wilson’s disease following the start of penicillamine therapy. Arch Neurol 1989; 46: 359-60.
- 30. Brewer GJ, Hedera P, Kluin KJ, Carlson M, Ascari F, Dick RB, et al. Treatment of Wilson disease with ammonium tetrathiomolybdate: III. Initial therapy in a total of 55 neurologically affected patients and follow-up with zinc therapy. Arch Neurol 2003; 60: 379-85.
- 31. Iorio R, D’Ambrosi M, Marcellini M, Barbera C, Maggiore G, Zancan L, et al. Serum transaminases in children with Wilson’s disease. J Pediatr Gastroenterol Nutr 2004; 39: 331-6.
- 32. Wiggelinkhuizen M, Tilanus ME, Bollen CW, Houwen RH. Systematic review: clinical efficacy of chelator agents and zinc in the initial treatment of Wilson disease. Aliment Pharmacol Ther 2009; 29: 947-58.
- 33. Burke JF, Dayalu P, Nan B, Askari F, Brewer GJ, Lorincz MT. Prognostic significance of neurologic examination findings in Wilson disease. Park Rel Disord 2011;17:551-6.
- 34. Hefter H, Tezayak O. Rosenthal D. Long-term outcome of neurological Wilson ́s disease. Parkinsonism Relat Disord 2018;49:48-53
Details
| Primary Language | Turkish |
|---|---|
| Subjects | Internal Diseases |
| Journal Section | ORIGINAL ARTICLES |
| Authors | |
| Publication Date | March 26, 2019 |
| Submission Date | October 30, 2018 |
| Published in Issue | Year 2019 Volume: 13 Issue: 2 |
The publication language of Turkish Journal of Pediatric Disease is English.
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