Syndromic variability of Wilson's disease in children. Clinical study of 44 cases

Abstract

Background: In children with Wilson's disease, no clinical or laboratory data are specific for diagnosis as in adult age.

Aim: Clinical aspects and parameters of copper metabolism in a large series of pediatric cases are evaluated to establish certain criteria for diagnosis and for correct treatment, even in difficult cases.

Methods: In 44 children with Wilson's disease, clinical aspects, histological features, laboratory parameters and data of copper metabolism have been studied. Forty patients, treated with penicillamine, were followed up (median 77 months).

Results: The 44 cases were classified as: asymptomatic forms (nine cases, six of them siblings of affected subjects), chronic hepatitis (23 cases), hepatocerebral manifestations (four cases), decompensated cirrhosis (six cases), fulminant hepatic failure with hemolytic anemia (two cases). Ceruloplasmin levels were abnormal in 37 out of 43 tested cases, but normal in six (14%) who showed high basal and after penicillamine load urine copper excretion and increased hepatic copper content. Urine copper concentration was pathological in 35 out of 42 tested cases (83%), but normal in seven patients under six years. Hepatic copper levels were very high in all the 20 tested patients. Under treatment, 27 children had favourable outcome. One patient showed no evolution of disease, seven patients worsened because of non-compliance to the therapy (one underwent successful liver transplantation) or severe side effects. Five patients with failure died.

Conclusions: Wilson's disease in children may present with a broad clinical spectrum, but the liver involvement is by far the most prevalent. The early diagnosis, based on clinical suspicion and results of copper metabolism investigation (including hepatic copper content evaluation in difficult cases) and appropriate treatment can prevent the progression of the disease.