Diagnostic Challenges of Wilson Disease in Early Childhood

Abstract

INTRODUCTION: Wilson’s Disease (WD) is an autosomal recessive inherited copper metabolism disorder caused by mutations in the ATP7B gene. The aim of this study was to retrospectively evaluate the patients diagnosed prior to the age of five. MATERIALS and METHODS: Between January 2005 and December 2018, the clinical and laboratory characteristics, treatment and prognostic features of 64 WD patients, 13 of whom were ≤ 5 years old, were analyzed retrospectively. RESULTS: Of the 64 patients in this study, 33 were male and the mean age at the time of diagnosis was 9.38 ± 3.37 years (3yr 5mo-16yr 3mo). Thirteen (20.3%) of these patients were ≤ 5 years of age (7 girls, 4.1 ± 0.6 years). Of patients ≤ 5 years of age 38.4% presented with hepatomegaly, 53.8% with similar family history, 76.9% with elevated AST and ALT levels, 76.9% with low ceruloplasmin level, 53.8% with increased urinary copper excretion, and 50% with an increased liver copper quantification. When patients ≤ 5 years of age compared with < 5 years of age patients at the time of admission, there was a statistically significant increment on AST levels but decrement in the levels of total bilirubin, direct bilirubin, and urinary copper (p=0.023, 0.009, p=0.040, p=0.011, respectively). Of patients ≤ 5 years of age (n =10) who underwent liver biopsy, mononuclear inflammatory cell infiltration (80%), macro-vesicular steatosis (50%), and parenchymal necrosis were observed in portal areas. While liver copper quantification was 405 ± 101.3 µg / gr in patients ≤ 5 years of age, that value evaluated as 615.9 ± 56,4 µg / g in patients > 5 years of age. The amount of liver copper quantification, framework distortion and bridging necrosis on liver biopsy were statistically at increased levels in patients > 5 years of age (p = 0.03, p = 0.01, p = 0.005, respectively). RESULTS: As seen in this study, the chance of early diagnosis of patients with WD increasing steadily. In countries like Turkey where consanguineous marriages are common, it is difficult to diagnose WD with a single test and many tests should be performed jointly CONCLUSIONS:. Early diagnosis and treatment having a great impact on prognosis. © 2020, Galenos Yayincilik,. All rights reserved.