Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang City, Liaoning Province, People's Republic of China.
BMC Pediatr. 2024 Sep 12;24(1):576. doi: 10.1186/s12887-024-05045-x.
Wilson disease (WD) is an autosomal recessive inherited disease caused by ATP7B variants and characterized by copper metabolism defects. However, children with WD are often asymptomatic, making the clinical diagnosis difficult. Therefore, more accurate methods are required for clinical diagnosis. The objective of this study was to highlight the phenotypic and genetic characteristics of children with WD in northeast China.
We retrospectively analyzed the clinical data and gene sequencing results of 65 children with WD from January 1, 2014, to December 31, 2022, at the Shengjing Hospital of China Medical University. All data refer to the time of diagnosis before treatment.
The median age at diagnosis was 5 years (range 1.2-15 years). In 50 cases (50/65, 76.9%) patients, routine physical examinations revealed only abnormal liver function. However, they had a significantly negative (p < 0.05) Kayser-Fleischer ring (KF). Children with acute liver failure had significantly increased 24 h urinary copper excretion (p < 0.05). We detected 46 genetic variants of ATP7B, including seven novel variants. The most frequent variant was p.R778L with an allele frequency of 38.7%. Phenotype-genotype correlation analysis suggested that p.R778L was significantly associated with lower serum ceruloplasmin levels and higher zinc levels (p < 0.05). The loss-of-function (LOF) variant was associated with significantly lower albumin levels (p < 0.05).
Most children with WD are asymptomatic, which makes early diagnosis of WD difficult. Therefore, clinical and laboratory characteristics as well as genetic testing are essential. p.R778L is the most frequent variant of ATP7B in China and may play an important role in lowering serum ceruloplasmin levels.
威尔逊病（WD）是一种常染色体隐性遗传疾病，由 ATP7B 变异引起，其特征为铜代谢缺陷。然而，WD 患儿常无症状，临床诊断困难。因此，需要更准确的方法进行临床诊断。本研究旨在强调中国东北地区 WD 患儿的表型和遗传特征。
我们回顾性分析了 2014 年 1 月 1 日至 2022 年 12 月 31 日在中国医科大学盛京医院就诊的 65 例 WD 患儿的临床资料和基因测序结果。所有数据均为治疗前诊断时的数据。
中位诊断年龄为 5 岁（范围 1.2-15 岁）。50 例（50/65，76.9%）患儿常规体检仅发现肝功能异常，但均有明显的阴性（p<0.05）Kayser-Fleischer 环（KF）。急性肝衰竭患儿 24 小时尿铜排泄量明显增加（p<0.05）。共检测到 ATP7B 46 种基因突变，包括 7 种新变异。最常见的变异是 p.R778L，等位基因频率为 38.7%。表型-基因型相关性分析表明，p.R778L 与血清铜蓝蛋白水平降低和锌水平升高显著相关（p<0.05）。功能丧失（LOF）变异与白蛋白水平显著降低相关（p<0.05）。
大多数 WD 患儿无症状，这使得 WD 的早期诊断变得困难。因此，临床和实验室特征以及基因检测至关重要。p.R778L 是中国 ATP7B 最常见的变异，可能在降低血清铜蓝蛋白水平方面发挥重要作用。
