Aggiornamento
Malattia di Wilson: dieci motivi per (ri)parlarne ai pediatri
Wilson disease: why talking about it
Raffaele Iorio, Giusy Ranucci, Daniela Liccardo, Maria Giovanna Puoti, Fabiola Di Dato
Dipartimento di Pediatria, Università Federico II, Napoli
Ottobre 2012 - pagg. 501 -507
Abstract
Wilson disease (WD) is an inherited autosomal recessive disorder of copper metabolism
characterized by progressive copper accumulation in the liver and then in other organs,
such as the nervous system, eyes and kidneys. In childhood, clinical presentation of WD
is usually characterized by signs of liver disease, while the typical neurological signs are
rarely observed. The hepatic clinical presentation ranges widely among different settings.
In Italy, the majority of the paediatric patients with WD are recruited following the detection
of isolated hypertransaminasemia. Early detection of WD is desirable in order to
avoid the dramatic progression of the hepatic and neurologic diseases. Unfortunately, early
diagnosis is a challenging task, especially in childhood, because the conventional criteria
established for adults are not always appropriate for children. The currently available
drugs are D-penicillamine and zinc, which act with different mechanisms. None of the available
drugs is side-effect-free. In this article the main key-points of diagnosis and management
of WD in paediatric patients are discussed.
Parole chiave
Suggerite dall'AI
Classificazione MeSH
Bibliografia
1. Maggiore G. La malattia di Wilson, una diagnosi
da non sbagliare. Medico e Bambino
1995;14:180-6.
2. Ala A, Walker AP, Ashkan K, Dooley JS,
Schilsky ML. Wilson’s disease. Lancet 2007;
369:397-408.
3. Zappu A, Magli O, Lepori MB, et al. High
incidence and allelic homogeneity of Wilson
disease in two isolated populations. A prerequisite
for efficient disease prevention programs.
J Pediatr Gastroenterol Nutr 2008;
47:334-8.
4. Tanzi RE, Petrukhin K, Chernov I, et al. The
Wilson disease gene is a copper transporting
ATPase with the Menkes disease gene. Nat
Genet 1993;5:344-50.
5. Bruha R, Marecek Z, Pospisilova L, et al.
Long-term follow-up of Wilson disease: natural
history, treatment, mutations analysis and phenotypic
correlation. Liver Int 2011;31:83-91.
6. Iorio R, D’Ambrosi M, Marcellini M, et al.
Persistence of eleveted aminotransferases in
Wilson’s disease despite adequate therapy.
Hepatology 2004;39:1173-4.
7. Nicastro E, Ranucci G, Vajro P, Vegnente A,
Iorio R. Re-evaluation of the diagnostic criteria
for Wilson disease in children with mild liver
disease. Hepatology 2010;52:1948-56.
8. Dhawan A, Taylor RM, Cheeseman P, De
Silva P, Katsiyiannakis L, Mieli-Vergani G. Wilson’s
disease in children: 37-Year experience
and revised King’s score for liver transplantation.
Liver Transpl 2005;11:441-8.
9. Sánchez-Albisua I, Garde T, Hierro L, et al.
A high index of suspicion: the key to an early
diagnosis of Wilson’s disease in childhood. J
Pediatr Gastroenterol Nutr 1999;28:186-90.
10. Schwimmer JB, Deutsch R, Kahen T, Lavine
JE, Stanley C, Behling C. Prevalence of
fatty liver in children and adolescents. Pediatrics
2006;118:1388-93.
11. Molleston JP, White F, Teckman J, Fitzgerald
JF. Obese children with steatohepatitis
can develop cirrhosis in childhood. Am J Gastroenterol
2002;97:2460-2.
12. 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;148:652-8.
13. Berman DH, Leventhal RI, Gavaler JS, Cadoff
EM, Van Thiel DH. Clinical differentiation
of fulminant Wilsonian hepatitis from
other causes of hepatic failure. Gastroenterology
1991;100:1129-34.
14. Ferenci P, Caca K, Loudianos G, et al. Diagnosis
and phenotypic classification of Wilson
disease. Liver Int 2003;23:139-42.
15. Hellman NE, Gitlin JD. Ceruloplasmin metabolism
and function. Annu Rev Nutr 2002;22:
439-58.
16. Nicastro E, Loudianos G, Zancan L, et al.
Genotype-phenotype correlation in Italian
children with Wilson’s disease. J Hepatol
2009;50:555-61.
17. Calvo PL, Pagliardini S, Baldi M, et al.
Long-standing mild hypertransaminasemia
caused by congenital disorder of glycosylation
(CDG) type IIx. J Inherit Metab Dis 2008;31:
S437-40.
18. Mandato C, Brive L, Miura Y, et al. Cryptogenic
liver disease in four children: a novel
congenital disorder of glycosylation. Pediatr
Res 2006;59:293-8.
19. Ferenci P, Steindl-Munda P, Vogel W, et al.
Diagnosti value of quantitative hepatic copper
determination in patients with Wilson’s disease.
Clin Gastroenterol Hepatol 2005;3:811-8.
20. Machado A, Chien HF, Deguti MM, et al.
Neurological manifestations in Wilson’s disease:
Report of 119 cases. Mov Disord 2006;
21:2192-6.
21. Lin JJ, Lin KL, Wang HS, Wong MC. Psychological
presentations without hepatic involvement
in Wilson disease. Pediatr Neurol
2006;35:284-6.
22. Oder W, Grimm G, Kollegger H, Ferenci P,
Schneider B, Deecke L. Neurological and neuropsychiatric
spectrum of Wilson’s disease: a
prospective study of 45 cases. J Neurol 1991;
238:281-7.
23. Lorincz MT. Neurologic Wilson’s disease.
Ann N Y Acad Sci 2010;1184:173-87.
24. Pfeiffer RF. Wilson’s Disease. Semin Neurol
2007;27:123-32.
25. 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.
26. Srinivas K, Sinha S, Taly AB, et al. Dominant
psychiatric manifestations in Wilson’s disease:
a diagnostic and therapeutic challenge!
J Neurol Sci 2008;266:104-8.
27. Wilson disease mutation database. http://
www.uofa-medical-genetics.org.
28. Brewer GJ, Yuzbasiyan-Gurkan V, Lee DY,
Appelman H. Treatment of Wilson’s disease
with zinc. VI. Initial treatment studies. J Lab
Clin Med 1989;114:633-8.
29. Weiss KH, Gotthardt DN, Klemm D, et al.
Zinc monotherapy is not as effective as chelating
agents in treatment of Wilson disease. Gastroenterology
2011;140:1189-98.
Corrispondenza: riorio@unina.it