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

Abstract

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 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). Conclusions: 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.

Adequate Chelation and Cupriuresis in Hepatic Wilson disease patients under Combination (Chelator + Zinc) therapy at 2 years of follow up

“…In another study the 2 year follow up UCE was 223.5mcg/day in the hepatic WD cases [8] but the authors have not analysed the statistical signi cance of the reduction in UCE. Moreover, the signi cant decrease in the UCE levels in the pediatric study [10] was seen at 3-4 years follow up as contrast to 2 years in the present study. Apart from small sample size of the cohort in the study [10], another plausible explanation for this difference in UCE between their cohorts and our cohort might be attributed to the better and prompt treatment response to the combination therapy used in our cohort as against the chelator monotherapy used by the previous mentioned studies.…”

“…In our cohort, the baseline mean UCE was 654.08 ± 803.78 mcg/day (Median (IQR): 332.0 (195.70-788.19) without any D-Pen challenge which is comparable with the values reported from other hepatic WD cohorts [8,10]. The observed decline in UCE at 2 year follow up compared to the baseline value was also in agreement with the ndings of the previous published literature [8,10]. Likewise, in a study from a German centre done among 321 WD patients [9], the author found signi cant decrease in UCE (performed after 48hour D-Pen dose interruption) at 1 and 2 year follow up visits.…”

“…Likewise, in a study from a German centre done among 321 WD patients [9], the author found signi cant decrease in UCE (performed after 48hour D-Pen dose interruption) at 1 and 2 year follow up visits. However, the 2 year follow up UCE rates were higher in the studies by Pfeiffenberger et al [9] and Chanpong et al [10] as compared to our cohort. Their 2 year UCE values (mcg/day) were [median: 507.5 (range: 277.2 -2290.2)] and [median: 587 (IQR: 217.8-831.6)] respectively, whereas in our study it was 307.5 (169.0-447.7) mcg/day.…”

“…UCE usually remains in the range of 200-500 mcg/day after 1-2 years of initiation of chelation therapy in the well-controlled compliant patients [8][9]. Till date, only one paediatric study has been published which suggests that there occurs a signi cant reduction in UCE after 1-2 years of treatment as compared to the pre-treatment values [10]. Furthermore, there is no published literature on the follow-up UCE values of the WD patients receiving combination therapy of a chelator and Zinc (Zn).…”

Wilson disease in children and young adults - State of the art

“…A recent study has proposed the use of 24-h urinary copper excretion to monitor adherence in children with WD. [ 76 ] This study suggested that the level of 24-h urinary copper should drop to ≤8 μmol/day and <6 μmol/day after 1 and 5 years of treatment, respectively.…”