Pediatric Wilson’s disease
findings in different presentations. A cross-sectional study
Keywords:
Hepatolenticular degeneration, Child, Zinc, IronAbstract
BACKGROUND: Wilson’s disease (WD) may present with different manifestations: from an asymptomatic state to liver cirrhosis. Here, we aimed to evaluate clinical presentations and laboratory findings and prog- noses among WD cases. DESIGN AND SETTING: Cross-sectional study based on patients’ records from the university hospital, İn- önü University, Malatya, Turkey. METHODS: The medical records of 64 children with WD were evaluated focusing on the clinical, laborato- ry and liver biopsy findings in different clinical presentations. RESULTS: The mean age at diagnosis was 8.6 ± 3.26 years (range 3.5-17) and mean length of follow-up was 2.49 years (range 0-9). There were 18 cases (28.1%), 12 (18.8%), 9 (14.1%) and 6 (9.4%) of chronic liver disease, fulminant liver failure, neurological WD and acute hepatitis, respectively. Nineteen (29.7%) were asymptomatic. The most common sign and laboratory finding were jaundice (45.3%) and hypertransam- inasemia (85.9%), respectively. The lowest serum zinc level was found in the fulminant liver failure group (P = 0.035). Hepatosteatosis was detected in 35% of the 20 patients who underwent liver biopsy. Among those with hepatosteatosis, 57.1% were asymptomatic. While 35% had copper staining, 25% presented iron accumulation in liver biopsies. Nine cases underwent liver transplantation and seven of these pre- sented fulminant liver failure (77.8%). CONCLUSION: The presentation, symptoms and signs of our cases were similar to those in previously reported series, except for the high proportion of fulminant WD cases. Further studies are needed to clarify the relationship between zinc levels and development of a fulminant course and between iron status and WD.
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References
Gitlin JD. Wilson disease. Gastroenterology. 2003;125(6):1868-77. PMID: 14724838; doi: 10.1053/j.gastro.2003.05.010.
Tao TY, Gitlin JD. Hepatic copper metabolism: insights from genetic disease. Hepatology. 2003;37(6):1241-7. PMID: 12773998; doi:10.1053/jhep.2003.50281.
Lutsenko S, Petris MJ. Function and regulation of the mammalian copper-transporting ATPases: insights from biochemical and cell biological approaches. J Membr Biol. 2003;191(1):1-12. PMID: 12532272; doi: 10.1007/s00232-002-1040-6.
Ferenci P. Regional distribution of mutations of the ATP7B gene in patients with Wilson disease: impact on genetic testing. Hum Genet. 2006;120(2):151-9. PMID: 16791614; doi: 10.1007/s00439-006-0202-5.
European Association for Study of Liver. EASL Clinical Practice Guidelines: Wilson’s disease. J Hepatol. 2012; 56(3):671-85. PMID: 22340672; doi: 10.1016/j.jhep.2011.11.007.
Roberts EA, Schilsky ML. American Association for Study of Liver Diseases (AASLD). Diagnosis and treatment of Wilson disease: an update. Hepatology. 2008;47(6):2089-111. PMID: 18506894; doi: 10.1002/hep.22261.
Rukunuzzaman M. Wilson’s disease in Bangladeshi children: analysis of 100 cases. Pediatr Gastroenterol Hepatol Nutr. 2015;18(2):121-7. PMID: 26157698; doi: 10.5223/pghn.2015.18.2.121.
Iorio R, D’Ambrosi M, Marcellini M, et al. Serum transaminases in children with Wilson’s disease. J Pediatr Gastroenterol Nutr. 2004;39(4):331-6. PMID: 15448420.
Manolaki N, Nikolopoulou G, Daikos GL, et al. Wilson disease in children: analysis of 57 cases. J Pediatr Gastroenterol Nutr. 2009;48(1):72-7. PMID: 19172127; doi: 10.1097/MPG.0b013e31817d80b8.
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):115-20. PMID: 16709660; doi: 10.1136/gut.2005.087262.
Ferenci P, Caca K, Loudianos G, et al. Diagnosis and phenotypic classification of Wilson disease. Liver Int. 2003;23(3):139-42. PMID: 12955875; doi: 10.1034/j.1600-0676.2003.00824.x.
Whitington PF, Alonso AE. Fulminant hepatitis and acute liver failure. In: Kelly DA, editor. Paediatric Liver Disease. Oxford: Blackwell; 2003. p. 107-26.
Squires RH Jr, Shneider BL, Bucuvalas J, et al. Acute liver failure in children: the first 348 patients in the pediatric acute liver failure study group. J Pediatr. 2006;148(5):652-8. PMID: 16737880; doi: 10.1016/j. jpeds.2005.12.051.
Machado A, Chien HF, Deguti MM, et al. Neurological manifestations in Wilson’s disease: Report of 119 cases. Mov Disord. 2006;21(12):2192-6. PMID: 17078070; doi: 10.1002/mds.21170.
Kleine RT, Mendes R, Pugliese R, et al. Wilson’s disease: an analysis of 28 Brazilian children. Clinics (Sao Paulo). 2012;67(3):231-5. PMID: 22473403; doi: 10.6061/clinics/2012(03)05.
Beyersdorff A, Findeisen A. Morbus Wilson: case report of a two-year-old child as first manifestation. Scand J Gastroenterol. 2006;41(4):496-7. PMID: 16635921; doi: 10.1080/00365520500389453.
Dhawan A, Taylor RM, Cheeseman P, et al. Wilson’s disease in children:
- year experience and revised King’s score for liver transplantation. Liver Transpl. 2005;11(4):441-8. PMID: 15776453; doi: 10.1002/lt.20352.
Magalhaes AC, Caramelli P, Menezes JR, et al. Wilson’s disease: MRI with clinical correlation. Neuroradiology. 1994;36(2):97-100. PMID: 8183467.
El-Karaksy H, Fahmy M, El-Raziky MS, et al. A clinical study of Wilson’s disease: The experience of a single Egyptian Paediatric Hepatology Unit. Arab J Gastroenterol. 2011;12(3):125-30. PMID: 22055589; doi: 10.1016/j.ajg.2011.07.007.
Van Biervliet S, Küry S, De Bruyne R, et al. Clinical zinc deficiency as early presentation of Wilson disease. J Pediatr Gastroenterol Nutr. 2015;60(4):457-9. PMID: 25825851; doi: 10.1097/MPG.0000000000000628.
Geetha A, Jeyachristy SA, Selvamathy SM, Ilavarasi S, Surendran R. A study on the concentrations of serum zinc, non-ceruloplasmin copper, reactive oxygen and nitrogen species in children with Wilson’s disease who had hepatic and neurological presentation. Clin Chim Acta 2007;383(1-2):165-7. Epub 2007 May 18. PubMed. PMID: 17573059; doi: 10.1016/j.cca.2007.05.005.
Iorio R, Ranucci G. Wilson’s disease: a matter of copper, but also of zinc. J Pediatr Gastroenterol Nutr. 2015;60(4):423-4. doi: 10.1097/MPG.0000000000000725.
Shiono Y, Wakusawa S, Hayashi H, et al. Iron accumulation in the liver of male patients with Wilson’s disease. Am J Gastroenterol 2001;96:3147-
PMID: 25611032; doi: 10.1111/j.1572-0241.2001.05269.
Hayashi H, Yano M, Fujita Y, Wakusawa S. Compound overload of copper and iron in patients with Wilson’s disease. Med Mol Morphol. 2006;39(3):121-6. PMID: 16998622; doi: 10.1007/s00795-006-0326-7.
