Salivary copper as a screening tool for pediatric Wilson's disease: A pilot study

Wilson's disease (WD) is a treatable disorder of copper metabolism in which early diagnosis remains challenging, particularly during the asymptomatic pediatric phase, limiting the feasibility of population-level screening strategies.

To assess the feasibility of salivary copper as a screening biomarker for pediatric WD and establish preliminary reference values in asymptomatic children.

In this cross-sectional pilot study, healthy children aged 5-15 years were recruited from pediatric outpatient clinics at a tertiary academic center. Salivary copper concentrations were quantified by ICP-MS, and percentile-based reference values were estimated. Associations with age and sex were assessed using multivariable linear regression with log10-transformed copper values. An exploratory post-hoc analysis integrating pediatric controls with patients with confirmed WD was performed using receiver operating characteristic (ROC) curve analysis.

A total of 114 children were included. Salivary copper concentrations showed a right-skewed distribution, with a median of 12.19 μg/L (IQR: 8.67-19.73 μg/L). The preliminary upper reference threshold was 30.73 μg/L after exclusion of extreme outliers. Salivary copper levels were not significantly associated with age or sex. In exploratory ROC analysis, salivary copper showed promising discriminative performance for WD (AUC 0.822, 95% CI 0.701-0.942). The Youden-derived cutoff (14.94 μg/L) showed higher sensitivity and moderate specificity, whereas higher thresholds demonstrated high specificity but lower sensitivity.

Salivary copper measurement is a feasible, non-invasive biomarker with potential application in pediatric WD screening. These findings support a dual-threshold strategy for screening and confirmatory assessment, although larger multicenter validation studies are required.