Clinical characteristics of Wilson’s disease in children

Wilson’s disease is an autosomal recessive disorder of copper metabolism caused by biallelic pathogenic variants in the ATP7B gene and associated with hepatic, neurological, psychiatric, and ophthalmological clinical manifestations. Objective. To determine the clinical characteristics and rates of liver cirrhosis development in children with Wilson’s disease. Patients and methods. The study included 204 children aged between 2.9 years and 17 years 11 months (boys – 99, girls – 105) with a confirmed diagnosis of Wilson’s disease. All patients underwent clinical and laboratory examinations, including clinical and biochemical blood tests, determination of daily urinary copper excretion (basal and after D-penicillamine challenge test), abdominal ultrasound, ultrasound-based liver elastography, examination by an ophthalmologist and a neurologist. Liver biopsy was performed in 72 patients. Molecular genetic blood testing was performed in 160 patients and 60 sibs. Results. The first clinical manifestations of Wilson’s disease in children were registered at the age of 7.0 [4.0;13.0] years, the age of diagnosis was 11.0 [8.5;14.0] years. Low serum levels of ceruloplasmin were recorded in 85.3% and copper in 46.2% of patients. The median daily urinary copper excretion was 122.1 [91;182] and 1608 [1145;2119] μg/day followed by D-penicillamine challenge test. According to the examination results, the hepatic form of Wilson’s disease was diagnosed in 81.4% and the mixed form in 18.6% of children. Cirrhosis developed in 29.4% of patients, with an average age of 14.0 [12.0;15.0] years. Kayser–Fleischer ring was determined in 29.9% of patients. In the ATP7B gene, the mutation NM_000053: c.3207C>A p. (His1069Gln) was detected in 77.2% at the homo- and heterozygous states. Conclusion. Early diagnosis of Wilson’s disease is crucial to prevent disease progression and the development of severe irreversible outcomes. Key words: children, Wilson’s disease, chronic hepatitis, fibrosis, liver cirrhosis