24小时尿铜用于儿童肝豆状核变性诊断的再评价

The reassessment of the diagnostic value of 24-hour urinary copper excretion in children with Wilson＇s disease

目的评价24h尿铜定量用于儿童肝豆状核变性（WD）的诊断价值，并探讨最佳诊断界值。方法收集本院2005年7月2007年6月以肝病收住院的≥3岁患儿的临床资料和24h尿液标本，疑似WD者年龄不限。采用电感耦合等离子体质谱仪测定尿液铜浓度，计算24h尿铜值。临床资料结合部分患儿的ATP7B基因外显子测序检测后行WD评分，根据评分结果分成WD组和非WD两组。结果采用SPSS13．0软件进行统计分析。对WD组和非WD组的尿铜指标行非参数检验；对所有病例的24h尿铜值作受试者工作特征曲线，并计算曲线下面积和界值。结果共94例患儿入选，14例患者借助基因检测准确分组，WD组和非WD组分别为26例和68例。WD组和非WD组患儿24h尿铜定量的中位数分别为98．5（18．3～1180．5）μg和25．8（1．4～357．9）μg，差异有统计学意义（Z=6．111，P=0．000）。24h尿铜定量的受试者工作特征曲线下面积为0．909（95％可信区间0.839～0．979，P=0．000）。敏感度、特异度、准确性、阳性预测值和阴性预测值，在取最佳界值52ug时分别为84．6％、91．2％、89．4％、78．6％和93．9％，取100μg界值时分别为50．0％、97．1％、84．0％、86．7％和83．5％。分别以24h尿铜界值52ug和100gg为诊断标准与WD评分法为金标准进行吻合度比较，52ug界值的整体吻合度高于100ug界点（符合度系数分别为0．760和0．541），且敏感度、准确性和阴性预测值均高于100ug界值，而特异度和阳性预测值较接近。结论24h尿铜52μg界值与100μg界值相比，可提高诊断儿童WD的敏感度和准确性。

Objective To reassess the diagnostic value of 24 hour urinary copper excretion in children with Wilson disease （WD）. Methods From July 2005 to June 2007, inpatients over three years old in a pediatric liver center were assigned into WD and non-WD group. Results 94 patients, including 26 cases in WD and 68 in non-WD group, were enrolled in this study. The median of 24 h urinary copper excretion was 98.5 lag in WD group and 25.8 μg in the non-WD group （Z = -6.111, P = 0.000）. The area under receiver operator curve （ROC） was 0.909 （95% CI： 0.839-0.979, P = 0.000）. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value were 84.6%, 91.2%, 89.4%, 78.6% and 93.9% respectively using 52.0ug as a cutoff value, and 50.0%, 97.1%, 84.0%, 86.7% and 83.5% using 100 μg as a cutoff value. The goodness of fitness of 52 lag criteria was significantly higher than 100 μg criteria （ k coefficient 0.760, 0.541 respectively, P equal to 0.000）. Conclusion Comparing to 100, 52μg of 24 h urinary copper excretion as a cutoff value significantly improves the sensitivity and accuracy for diagnosing WD in children.