Long-Term Urinary Copper Excretion on Chelation Therapy in Children with Wilson Disease

In Wilson disease (WD), 24-hour urinary copper excretion (UCE) is recommended to be used for diagnosis. It may be a useful tool to assess the efficacy of treatment during follow-up; however, there are limited data regarding the cutoff value of 24-hour UCE during follow-up in children. Therefore, we aim to evaluate the clinical use of 24-hour UCE during follow-up in children with WD.

Medical records of children diagnosed with WD at Kings' College Hospital from 2005 to 2018 were retrospectively reviewed. The UCE, serum copper, and ceruloplasmin levels, tested during follow-up, were statistically analyzed.

Over the median duration of 7 years (range 1.4-14.4), 28 patients (age ranged 3.8-17.3 years) had UCE tests during follow-up. Of those, 21 patients had at least one 24-hour UCE test and 7 children had only spot UCE tests. In comparison with the level of 24-hour UCE collected at the first visit after penicillamine challenge test, the median excretion rate was significantly reduced over the follow-up period (P < 0.001), from 26.2 to 8.9 μmol/day following 1-2 years of therapy (P = 0.15), then reduced significantly to 2.2 μmol/day after 3-4 years (P = 0.009), and 5.6 μmol/day at >5 years of follow-up (P = 0.003).

Our study suggests that within 1 year of treatment, the level of nonceruloplasmin-bound copper concentration (NCC) drops to <0.8 μmol/L. In the absence of progressive liver disease or signs of copper deficiency, 24-hour UCE decreases to ≤8 μmol/day and <6 μmol/day after 1 and 5 years of treatment, respectively.