Document Type : original article


1 Department of Pediatric Gastroenterology, Ghaem Medical Center, Mashhad University of medical sciences, Mashhad, Iran.

2 Department of Pediatrics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

3 Department of Gastroenterology,Faculty of medicine,Mashhad university of medical sciences,Mashhad,Iran

4 Department of Pediatrics, Ghaem Medical Center, Mashhad University of medical sciences, Mashhad, Iran.

5 Clinical Research Development Center, Akbar Hospital, Faculty of Medicine, Mashhad University of medical sciences, Mashhad, Iran

6 Department of Pediatrics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran


Background: Early diagnosis and treatment of Wilson's disease in childhood can reduce long-term and life-threatening complications in these patients. Considering the lack of a database of Wilson's patients in Iranian patients, the present study was carried out with the primary objective of determining clinical and laboratory presentations in children with Wilson's disease referred to Akbar Hospital in Mashhad.
Methods: This cross-sectional descriptive study was conducted on children under 18 years of age with Wilson's disease who had presented to Akbar Children's Hospital in Mashhad during 2018-2019. The acquired information included demographic information, primary clinical symptoms (hepatic, cerebral, and psychological symptoms), and laboratory findings, including liver laboratory profile (AST, ALT, and ALP tests), coagulation tests, albumin, total serum protein, and direct and indirect bilirubin, and Wilson's diagnostic tests.
Results: In total, 25 patients with an average age of 15.88±4.54 years were included in this study. Hepatosplenomegaly, Kayser–Fleischer ring, and jaundice were observed in 72%, 68%, and 48% of patients, respectively. Gender of patients was not significantly correlated with the clinical and laboratory findings of Wilson’s disease (P<0.05). 24-hour urine copper level was higher than 100 micrograms in 82.6% of patients. Serum ceruloplasmin level was lower than 200 mg/liter in 90% of patients. Serum ceruloplasmin levels in patients with ascites (P=0.04) and patients with lower limb edema (P=0.02) were higher than those in patients without these findings. Moreover, a lower 24-hour urinary copper level was detected in patients with seizures (P=0.03), and patients with depression (P=0.005) compared to patients without these conditions. The 24-hour urine copper levels were higher in patients with jaundice than in those without jaundice (P=0.01).
Conclusion: Hepatosplenomegaly, Kayser–Fleischer ring, and jaundice are common symptoms in under 18-year-old patients with Wilson's disease. Considering the findings regarding the high levels of serum ceruloplasmin and copper in 24-hour urine in a significant 


  1. Compston A. Progressive lenticular degeneration: a familial nervous disease associated with cirrhosis of the liver. Brain. 1912; 34:295-509.
  2. Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J. Harrison's principles of internal medicine, 19e: Mcgraw-hill New York, NY, USA:; 2015.
  3. Rodriguez-Castro KI, Hevia-Urrutia FJ, Sturniolo GC. Wilson's disease: A review of what we have learned. World journal of hepatology. 2015; 7(29):2859-70.
  4. Gomes A, Dedoussis GV. Geographic distribution of ATP7B mutations in Wilson disease. Annals of human biology. 2016; 43(1):1-8.
  5. Bandmann O, Weiss KH, Kaler SG. Wilson's disease and other neurological copper disorders. The Lancet Neurology. 2015; 14(1):103-13.
  6. Kleinman RE, Goulet O-J, Mieli-Vergani G, Sanderson IR, Sherman PM, Shneider BL. Walker's pediatric gastrointestinal disease: physiology, diagnosis, management: PMPH USA, Ltd; 2018.
  7. Suchy FJ, Sokol RJ, Balistreri WF, Bezerra JA, Mack CL, Shneider BL. Liver disease in children: Cambridge University Press; 2021.
  8. Wyllie R, Hyams JS, Kay M. Pediatric gastrointestinal and liver disease E-Book: Elsevier Health Sciences; 2020.
  9. Xie J-J, Wu Z-Y. Wilson’s disease in China. Neuroscience bulletin. 2017; 33(3):323-30.
  10. Boga S, Ala A, Schilsky ML. Hepatic features of Wilson disease. Handbook of clinical neurology. 2017; 142:91-9.
  11. 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.
  12. 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):334-44.
  13. Manolaki N, Nikolopoulou G, Daikos GL, Panagiotakaki E, Tzetis M, Roma E, Kanavakis E, Syriopoulou VP. Wilson disease in children: analysis of 57 cases. Journal of pediatric gastroenterology and nutrition. 2009; 48(1):72-7.
  14. Dehghani SM, Erjaee A, Imanieh MH, Haghighat M, Bajalli Z, Malekpour A. Clinical and Paraclinical Features of Wilson’s Disease in Children in Shiraz, Southern Iran. Galen Medical Journal. 2014; 3(66-160: 3)
  15. Hefter H, Tezayak O, Rosenthal D. Long-term outcome of neurological Wilson's disease. Parkinsonism & Related Disorders. 2018; 49:48-53.
  16. Hedera P. Wilson's disease: A master of disguise. Parkinsonism & related disorders. 2019; 59:140-5.
  17. Cheung K-S, Seto W-K, Fung J, Lai C-L, Yuen M-F. Epidemiology and natural history of primary biliary cholangitis in the Chinese: a territory-based study in Hong Kong between 2000 and 2015. Clinical and translational gastroenterology. 2017; 8(8):e116.
  18. 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):1-20.
  19. Wiernicka A, Dądalski M, Jańczyk W, Kamińska D, Naorniakowska M, Hüsing-Kabar A, Schmidt H, Socha P. Early onset of Wilson disease: diagnostic challenges. Journal of pediatric gastroenterology and nutrition. 2017; 65(5):555-60.
  20. Kumagi T, Horiike N, Michitaka K, Hasebe A, Kawai K, Tokumoto Y, Nakanishi S, Furukawa S, Hiasa Y, Matsui H, Kurose K, Matsuura B, Onji M. Recent clinical features of Wilson’s disease with hepatic presentation. Journal of gastroenterology. 2004; 39(12):1165-9.
  21. Liver EAFTSOT. EASL clinical practice guidelines: Wilson’s disease. Journal of hepatology. 2012; 56(3):671-85.
  22. Steindl P, Ferenci P, Dienes H, Grimm G, Pabinger I, Madl C, Maier-Dobersberger T, Herneth A, Dragosics B, Meryn S, Knoflach P, Granditsch G, Gangl A. Wilson's disease in patients presenting with liver disease: a diagnostic challenge. Gastroenterology. 1997; 113(1):212-8.
  23. Gow PJ, Smallwood R, Angus PW, Smith A, Wall A, Sewell RB. Diagnosis of Wilson's disease: an experience over three decades. Gut. 2000; 46(3):415-9.
  24. Lin L-J, Wang D-X, Ding N-N, Lin Y, Jin Y, Zheng C-Q. Comprehensive analysis on clinical features of Wilson’s disease: an experience over 28 years with 133 cases. Neurological research. 2014; 36(2):157-63.
  25. 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 1. Liver International. 2003; 23(3):139-42.