Mini reviewWilson disease: What is still unclear in pediatric patients?
Introduction
Wilson's disease (WD) is an autosomal-recessive human copper (Cu) storage disorder caused by mutations in the ATP7B gene [1]. Clinical presentation can vary widely, but the key features of WD are liver disease and neuropsychiatric disturbances [2], [3]. Diagnosis of WD remains a challenging patchwork involving clinical, laboratory, histological and molecular tools [4]. The therapeutic success using oral copper chelating agents and zinc therapy makes WD one of the few treatable metabolic liver diseases.
Section snippets
Genetics and pathogenesis
The ATP7B gene is large and encodes copper-translocating ATPase expressed primarily in the liver. ATP7B resides in the trans-Golgi membrane compartment and mainly loads Cu on newly synthesized apoceruloplasmin [5]. The exact mechanism of copper hepatotoxicity and brain injury remains unclear. It is suggested that copper metabolism disturbance in WD is associated with significant changes in systemic antioxidant capacity parameters in a direction favoring enhanced oxidative stress [6].
To date,
Clinical features
Although the failure to excrete biliary copper is present from birth, WD symptoms generally do not develop until about three years of age, and rarely become evident before age of five. Unfortunately, symptoms at any age are frequently non-specific. Most of the pediatric WD patients present with liver disease, whereas neuropsychiatric symptoms are more common after the age of 18 years [15].
The hepatic clinical presentation ranges widely from asymptomatic hypertransaminasemia and/or fatty liver
Diagnosis
If WD is not recognized and adequately treated, the progression of hepatic and neurologic damage can be very rapid and ALF can occur. Therefore, the prompt detection of this condition is vital. Unfortunately, the diagnosis of WD is an especially challenging task [17].
In 2003, Ferenci et al [20] proposed a diagnostic score for WD, including clinical, biochemical, histologic and molecular findings. Table 1 shows scoring system clarifying for each item the diagnostic validated cutoff in pediatric
Treatment
The overall therapeutic aim for WD is the generation of a negative copper balance. Today this can be achieved either by liver transplantation, which phenotypically corrects the gene defect in the liver, or by medical therapy. Obviously liver transplantation is a treatment option for patients with severe life-threatening conditions in whom the window for medical treatment is not wide enough. It cannot be proposed as a therapeutic strategy, given the high rate of complications and the need for
Disclosure of interest
The authors declare that they have no conflicts of interest concerning this article.
Funding source: no funding was secured for this study.
Financial disclosure: authors have no financial relationships relevant to this article to disclose.
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Measurement of copper content in biological specimens
2017, Revista del Laboratorio ClinicoThe role of zinc in liver cirrhosis
2016, Annals of HepatologyCitation Excerpt :Zinc is suitable for maintenance treatment as well treatment of pre-symptomatic patients, pregnant patients and children.98 Zinc is also indicated as maintenance therapy for patients with Wilson’s disease initially treated with chelators, and as first- line therapy for patients with neurological onset.97,99 Patient’s serum or plasma zinc concentrations and urinary copper excretion should be monitored every six to eight weeks.
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