Mohr Isabelle, Lamade Patrick, Weber Christophe, Leidner Viola, Köhrer Sebastian, Olkus Alexander, Lang Matthias, Langel Andrea, Dankert Patrischia, Greibich Melanie, Wolf Silke, Zimmer Holger, Michl Patrick, Poujois Aurélia, Weiss Karl Heinz, Merle Uta
Internal Medicine IV, Department of Gastroenterology, University Hospital Heidelberg, INF 410, Heidelberg, 69120, Germany.
Internal Medicine III Department of Internal Medicine and Cardiology, University Hospital Heidelberg, Heidelberg, Germany.
Orphanet J Rare Dis. 2025 Jan 21;20(1):33. doi: 10.1186/s13023-025-03545-2.
BACKGROUND & AIM: Twenty-four-hour urinary copper excretion (24 h-UCE) is the standard diagnostic tool for dose adjustments in maintenance therapy in Wilson disease (WD) patients. Guidelines lack data if both variants of 24 h-UCE measurement (with or without 48 h of treatment interruption) are equally interpretable.
Eighty-four patients with a confirmed diagnosis of WD treated with chelators (50% of patients with D-Penicillamine and 50% with trientine) and with pairwise 24-h-UCE values on-therapy and off-therapy were included in the analysis. Pairwise urinary sampling between October 2022 (T0) and a 12-month FU (T2) was compared, and exchangeable copper (CuEXC) was additionally measured at T0.
Among the 84 patients, 65% had predominant hepatic symptoms, the median age was 42 years, and 58% were female. At T0, patients were in the stable maintenance phase, with a median treatment duration of 21.9 years. The levels of the biochemical markers liver and copper metabolism remained stable over the 12-month observation period for all patients. 24 h-UCE off-therapy significantly decreased from T0 to T2 (p = 0.03), whereas no statistically significant differences were detected for 24 h-UCE after therapy. Both sampling methods did not correlate. CuEXC was significantly correlated with 24 h-UCE after 48 h of dose interruption (p = 0.018) but not with 24 h-UCE after therapy. A total of 46% of the 24 h-UCE value pairs were discordant, laying out the aimed therapeutic ranges given in current international guidelines.
Off-therapy 24 h-UCE reflects the "free" copper pool more accurately than does urinary sampling. The study shows discordant results for both sampling methods in approximately half of the patients, revealing that interpretation of 24 h-UCE with respect to chelator-dosing decisions should be performed with caution.
24小时尿铜排泄量（24 h-UCE）是威尔逊病（WD）患者维持治疗中剂量调整的标准诊断工具。目前的指南缺乏关于24 h-UCE测量的两种方法（治疗中断48小时与否）是否同样具有可解释性的数据。
纳入84例确诊为WD且接受螯合剂治疗的患者（50%使用青霉胺，50%使用曲恩汀），分析其治疗期间和治疗中断后的成对24小时尿铜排泄量数据。比较2022年10月（T0）至12个月随访期（T2）的成对尿液样本，并在T0时额外测量可交换铜（CuEXC）。
84例患者中，65%以肝脏症状为主，中位年龄为42岁，58%为女性。在T0时，患者处于稳定的维持治疗阶段，中位治疗时长为21.9年。在12个月的观察期内，所有患者的肝脏和铜代谢生化标志物水平保持稳定。治疗中断后的24 h-UCE从T0到T2显著降低（p = 0.03），而治疗后的24 h-UCE未检测到统计学显著差异。两种采样方法不相关。剂量中断48小时后的CuEXC与24 h-UCE显著相关（p = 0.018），但与治疗后的24 h-UCE不相关。24 h-UCE值对中共有46%不一致，超出了当前国际指南给出的目标治疗范围。
治疗中断后的24 h-UCE比尿液采样更准确地反映“游离”铜池。该研究显示，约半数患者的两种采样方法结果不一致，提示在根据24 h-UCE进行螯合剂剂量决策时应谨慎。
