Persistently and asymptomatic raised liver enzymes as a form of presentation of Wilson's disease at pediatric age


  • Catarina Matos Pediatric Gastroenterology Service, Department of Child and Adolescence, Centro Hospitalar do Porto
  • Sofia Martins Pediatric Service of Hospital de São Pedro Vila Real, Centro Hospitalar Trás-os‑Montes e Alto Douro
  • Idolinda Quintal Pediatric Service of Hospital Padre Américo, Centro Hospitalar Tâmega e Sousa
  • Lucília Vieira Pediatric Service of Hospital Padre Américo, Centro Hospitalar Tâmega e Sousa
  • Francisca Costa Pathologic Anatomy Service of Hospital de Santo António, Centro Hospitalar do Porto
  • Fernando Pereira Pediatric Gastroenterology Service, Department of Child and Adolescence, Centro Hospitalar do Porto
  • Ermelinda Santos Silva Pediatric Gastroenterology Service, Department of Child and Adolescence, Centro Hospitalar do Porto



Wilson´s disease, D-penicilamine, raised liver enzymes, fatty liver children, copper metabolism


Background: Wilson`s disease is a rare autosomal recessive disorder characterized by a change in the transport of copper in the liver, with progressive accumulation in this and other organs such as brain, kidney and cornea. Phenotypic expression of the disease varies widely and can range from elevated liver enzymes, fatty liver or gallstones in asymptomatic patients, to cirrhosis and fulminant hepatic failure, or disabling neuropsychiatric disease.

Aim: To characterize a sample of patients with Wilson´s disease.

Patients and Methods: Retrospective survey including children diagnosed with Wilson´s disease between 2002 and 2011 according to the criteria of the European Association for the Study of the Liver (2012). We analyzed family history; age, clinical data, imaging and histology at the time of diagnosis; genetic analysis; treatment and side effects; follow-up and current status.

Results: We identified five patients. Three had a family history of disease. All were asymptomatic and had maintained raised liver enzymes. No patient had clinical stigmata of chronic liver disease. One female patient had overweight. All were treated with D-penicillamine, withdrawn in two patients because of side effects. Currently all patients remain asymptomatic, without evidence of progression of liver disease, with a median follow-up of 5 years and 3 months.

Discussion: Our series show that Wilson´s disease may be present with raised liver enzymes in asymptomatic children. The overweight patient alerts us to screen the disease in overweight/obese patients with raised liver enzymes and/or steatosis persisting for more than six months after weight loss.


Download data is not yet available.


Scheinberg IH, Sternlieb I. Wilson’s disease. In: Smith Jr LH, editor. Major problems in internal medicine, vol. 23. Philadelphia, PA: WB Saunders;1984. p. 25-35.

Tao TY, Gitlin JD. Hepatic copper metabolism: insights from genetic disease. Hepatology 2003;37:1241-7.

Lutsenko S, Petris MJ. Function and regulation of the mammalian coppertransporting ATPases: insights from biochemical and cell biological approaches. J Membr Biol 2003;191:1-12.

Wilson DC, Phillips MJ, Cox DW, Roberts EA. Severe hepatic Wilson’s disease in preschool-aged children. J Pediatr 2000;137:719-22.

Roberts EA, Schilsky ML. A practice guideline on Wilson disease. Hepatology 2003;37:1475-92.

Roberts EA, Schilsky ML. Diagnosis and Treatment of Wilson Disease: An Update. Hepatology 2008; 47 (6): 2090-105.

Ferenci P, Czlonkowska A, Stremmel W, Houwen R, Rosenberg W, Schilsky M, et al. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Wilson’s disease. Journal of Hepatology 2012; 56: 671-85.

Sánchez-Albisua I, Garde T, Hierro L, Camarena C, Frauca E, de la Vega A, Díaz MC, Larrauri J, Jara P. A high index of suspicion: the key to an early diagnosis of Wilson’s disease in childhood. J Pediatr Gastroenterol Nutr. 1999; 28 (2): 186-90.

Benhamla T, Tirouche YD, Abaoub-Germain A, Theodore F. The onset of psychiatric disorders and Wilson’s disease. Encephale. 2007; 33 (6): 924-32.

Nanda K. Non-alcoholic steatohepatitis in children. Pediatr Transplant. 2004;8 (6): 613-8.

Bramlage KS, Bansal V, Xanthakos SA, Kohli R. Fatty Liver Disease in Children-What Should One Do? Indian J Pediatr. 2012.

Pena-Quintana L, García-Luzardo M, García-Villarreal L, Arias-Santos M et al. Manifestations and Evolution of Wilson Disease in Pediatric Patients Carrying ATP7B Mutation L708P. JPGN 2012; 54 (1):48-54.

Iorio R, D’Ambrosi M, Marcellini M, Barbera C, Maggiore G et al. Serum Transaminases in Children with Wilson’s Disease. J Pediatr Gastroenterol Nutr. 2004; 39 (4): 331-6.

Manolaki N, Nikolopoulou G, Daikos GL, Panagiotakaki E, Tzetis M. Wilson disease in children: analysis of 57 cases. J Pediatr Gastroenterol Nutr. 2009; 48(1): 72-7.

Koppikar S, Dhawan A. Evaluation of the scoring system for the diagnosis of Wilson’s disease in children. Liver Int 2005;25:680-1.

Lykavieris P, Ducot B, Lachaux A, Dabadie A, Broue P, Sarles J,et al. Liver disease associated with ZZ a1-antitrypsin deficiency and ursodeoxycholic acid therapy in children. J Pediatr Gastroenterol Nutr 2008; 47 (5): 623-9.

Santos Silva E, Sarles J, Buts JP, Sokal EM. Successful medical treatment of severely decompensated Wilson disease. J Pediatr. 1996; 128:285-7.

Członkowska A, Litwin T, Karliński M, Dziezyc K, Chabik

G, Czerska M.D-penicillamine versus zinc sulfate as first-line

therapy for Wilson`s disease. Eur J Neurol. 2014 Jan 21. doi:

1111/ene.12348. [Epub ahead of print].

S, Taly AB. Withdrawal of penicillamine from zinc sulphatepenicillamine maintenance therapy in Wilson`s disease: promising, safe and cheap. J Neurological Sciences 2008; 264 (1): 129-32.

Weiss KH, Gotthardt DN, Klemm D, Merle U, Ferenci- Foerster D, Schaefer M, et al. Zinc monotherapy is not as effective as chelating agents in treatment of Wilson disease. Gastroenterology. 2011 Apr;140(4):1189-1198.e1. doi:10.1053/j.gastro.2010.12.034. Epub2010 Dec 24.

Wiernicka A, Jańczyk W, Dądalski M, Avsar Y, Schmidt H, Socha P. Gastrointestinal side effects in children with Wilson`s disease treated with zinc sulphate. World J Gastroenterol 2013; 19(27): 4356-62.

Ritchie SK, Murphy E, Ice C, Cottrell LA, Minor V, Elliot E, et al. Universal Versus Targeted Blood Cholesterol Screening Among Youth: The CARDIAC Project. Pediatrics 2010; 126 (2): 260-5.



How to Cite

Matos C, Martins S, Quintal I, Vieira L, Costa F, Pereira F, Silva ES. Persistently and asymptomatic raised liver enzymes as a form of presentation of Wilson’s disease at pediatric age. REVNEC [Internet]. 2015Jun.15 [cited 2024Feb.24];24(2):56-63. Available from:



Original Articles

Most read articles by the same author(s)

1 2 > >>