Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Rd, Guangzhou, 510623, China.
BMC Gastroenterol. 2022 Mar 16;22(1):124. doi: 10.1186/s12876-022-02186-0.
Serum ceruloplasmin is one of the major diagnostic parameters for Wilson's disease (WD). Age and gender difference of serum ceruloplasmin remain controversy. This study aims to assess diagnostic value of serum ceruloplasmin level for WD in children up to age of 15 years.
Serum ceruloplasmin levels were measured in 317 WD patients, 21 heterozygotes, 372 healthy control children and 154 non-WD patients with other liver diseases. Receiver operating characteristic (ROC) curve was used to determine the diagnostic accuracy of serum ceruloplasmin for WD in children.
Among healthy controls, serum ceruloplasmin level was slightly low in the infants younger than 6 months, and then maintained from 26 to 33 mg/dl after age of 6 months. A total of 8.1% of healthy children had levels of serum ceruloplasmin < 20 mg/dL. Serum ceruloplasmin level was 5.7 ± 4.7 mg/dl in WD patients, and 25.6 ± 5.9 mg/dl in heterozygous carriers. Only 1.9% of WD patients had serum ceruloplasmin levels > 20 mg/dL. Serum ceruloplasmin levels had gender difference, being higher in healthy boys than healthy girls, and higher in asymptomatic WD boys than asymptomatic WD girls (p < 0.01, p < 0.05). Serum ceruloplasmin levels also presented genotypic difference. WD patients with R778L homozygotes exhibited lower levels of serum ceruloplasmin than the patients without R778L (p < 0.05). The ROC curve revealed that serum ceruloplasmin level, at a cutoff value of 16.8 mg/dL, had the highest AUC value (0.990) with a sensitivity of 95.9% and a specificity of 93.6%.
Serum ceruloplasmin is one of sensitive diagnostic biomarkers for WD in children. Gender and genotypic difference of serum ceruloplasmin level should be considered. The cutoff value of serum ceruloplasmin level < 16.8 mg/dL may provide the highest accuracy for diagnosis of WD in children.
血清铜蓝蛋白是诊断威尔逊病（WD）的主要诊断参数之一。血清铜蓝蛋白在年龄和性别上的差异仍存在争议。本研究旨在评估血清铜蓝蛋白水平对 15 岁以下 WD 患儿的诊断价值。
测定 317 例 WD 患者、21 例杂合子、372 例健康对照儿童和 154 例其他肝病非 WD 患者的血清铜蓝蛋白水平。采用受试者工作特征（ROC）曲线确定血清铜蓝蛋白对儿童 WD 的诊断准确性。
在健康对照组中，6 个月以下婴儿的血清铜蓝蛋白水平略低，6 个月后维持在 26-33mg/dl。共有 8.1%的健康儿童血清铜蓝蛋白水平<20mg/dL。WD 患者的血清铜蓝蛋白水平为 5.7±4.7mg/dl，杂合子携带者为 25.6±5.9mg/dl。只有 1.9%的 WD 患者血清铜蓝蛋白水平>20mg/dL。血清铜蓝蛋白水平存在性别差异，健康男孩高于健康女孩，无症状 WD 男孩高于无症状 WD 女孩（p<0.01，p<0.05）。血清铜蓝蛋白水平也存在基因型差异。R778L 纯合子 WD 患者的血清铜蓝蛋白水平低于无 R778L 患者（p<0.05）。ROC 曲线显示，血清铜蓝蛋白水平在截断值为 16.8mg/dL 时具有最高 AUC 值（0.990），灵敏度为 95.9%，特异性为 93.6%。
血清铜蓝蛋白是儿童 WD 的一种敏感诊断生物标志物。应考虑血清铜蓝蛋白水平的性别和基因型差异。血清铜蓝蛋白水平<16.8mg/dL 的截断值可能为儿童 WD 的诊断提供最高的准确性。
