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

Objectives: 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. Patients and Methods: 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. Results: 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 mu mol/day following 1-2 years of therapy (P = 0.15), then reduced significantly to 2.2 mu mol/day after 3-4 years (P = 0.009), and 5.6 mu mol/day at >5 years of follow-up (P = 0.003). Conclusions: Our study suggests that within 1 year of treatment, the level of nonceruloplasmin-bound copper concentration (NCC) drops to <0.8 mu mol/L. In the absence of progressive liver disease or signs of copper deficiency, 24-hour UCE decreases to <= 8 mu mol/day and <6 mu mol/day after 1 and 5 years of treatment, respectively.