Background Wilson disease (WD) is a rare but commonly under-diagnosed inherited metabolic disease. Patients who are diagnosed early before disease onset (pre-symptomatic WD) have a good response to treatment. For universal screening in children, spot urine tests are more feasible than 24-hour urine collection. We previously established reference ranges for spot urine copper excretion indices. Here, we evaluated their screening performance in a prospective cohort of school children.

Methods Two samples of spot urine and one 24-hour urine were collected from 193 healthy Hong Kong children aged 4-11 years. Urine copper was measured by Inductively coupled plasma mass spectrometry (ICP-MS). Previously established screening cut-off values were evaluated: spot urine copper ≥0.5 µmol/L, copper to osmolality ratio ≥0.00085 μmol/mOsm, and copper to creatinine ratio ≥0.1 µmol/mmol together with a new step cut-off according to urine osmolality. Children whose urine sample exceeded any one cut-off value were called back for blood ceruloplasmin and copper as second-tier tests together with diagnostic sequencing of the ATP7B gene.

Results 10 children (5%) had second-tier testing. Two children had very low ceruloplasmin levels and were genetically confirmed to have WD. Both were completely asymptomatic at diagnosis. Spot urine copper concentration ≥0.5 µmol/L showed the best screening performance with excellent sensitivity. The strong correlation between spot urine copper concentration and 24-hour urine copper excretion (R²=0.83, p<0.01) provided the basis for screening WD by spot urine copper. In addition, one carrier was found among the call-back group who had normal plasma ceruloplasmin.

Conclusions In this small prospective screening cohort, 2 WD patients and 1 carrier were diagnosed. Spot urine copper is a useful biomarker for universal WD screening in school children, which may improve disease outcome and fundamentally change the natural history of WD by enabling early detection and therapy before symptom onset.

The authors have declared no competing interest.

This study was funded by Health and Medical Research Fund: PR-HKCH-10

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