Mutation analysis of ATP7B gene in Czech families with Wilson´sdisease.

BACKGROUND:Wilson´s disease (WD, MIM #277900) is an autosomal recessive genetic disorder of copper metabolism, caused by mutations in the ATP7B gene (13q14.3). The aim of our study was to analyse clinical presentations and diagnostic tests of pediatric patients with WD. METHODS:Retrospectively we analyzed the medical history of 35 patients (aged 17 months to 19 years) with confirmed diagnosis of WD treated at our institute from 2002 till March 2019. RESULTS:The mean onset of symptoms was 9.9 years of age. Of the patients 30 suffered from the hepatic form of the disorder (more frequently increased transaminases) and 5 from the mixed form (hepatic and neurologic or psychiatric form); 4 girls underwent orthotopic liver transplantation (OLT) due to acute failure of the liver. In 77.5 % cases the ceruloplasmin serum concentrations were ≤0.2g/l [median 0.16 (0.02;0.28)]. In 72.5% patients basal urinary copper excretion was ≥1.6µmol/24 hours [median 2.3(0.82;15.4)]. Mutation analysis was performed in all cases. The detection mutation ratio was 95.7%. We identified 2 novel ATP7B gene mutations [c.2732C>T;(p.A911V); c.2324C>T;(p.A775V)] and 18 known mutations. The most common mutation was c.3207C>A;(p.H1069Q) (53.7%). DISCUSSION:Conventional diagnostic criteria established for adults are commonly agreed for children but may not always be appropriate in the very young. Genetic testing is the most accurate and effective diagnostic method for early diagnosis.