Phenotypic and Genetic Characterization of children with Wilson Disease from Northeast China

AbstractBackground Wilson's disease (WD) is an autosomal recessive genetic disease caused by ATP7B gene mutations and characterized by copper metabolism disorders. Objective This study aimed to highlight the phenotypic and genetic characteristics of children with WD in Northeast China. Methods We retrospectively analyzed clinical data and gene sequencing results of 65 children with WD from January 1, 2014 to December 31, 2022 in Shengjing Hospital of China Medical University. Results The mean age at the time of the diagnosis of WD was 6.3 ± 3.52 years (range 1.2–15 years). Fifty cases (50/65, 76.9%) were asymptomatic and only found abnormal liver function during physical examination. However, they had negative Kayser–Fleischer (KF) ring with significant difference (p < 0.05). Children with acute liver failure had significantly elevated 24hr urinary Cu excretion (p < 0.05). We detected a total of 46 gene mutations in ATP7B gene, including 7 novel mutations. The most frequent mutation was p.R778L with an allelic frequency of 38.7%. Phenotype–genotype correlation analysis suggested that p.R778L was significantly associated with lower levels of serum ceruloplasmin and higher zinc levels (p < 0.05). LOF (loss of function) mutation was significantly associated lower albumin (p < 0.05). Conclusion Most children with WD are asymptomatic, which makes early diagnosis of WD challenging, and it is necessary to perform genetic test. p.R778L is the most frequently mutation of ATP7B gene in China and may play an important role in lower levels of serum ceruloplasmin.