Department of Clinical Biochemistry, Aarhus University Hospital, Palle Juul Jensens Boulevard 99, 8200 Aarhus N, Denmark.
Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul Jensens Boulevard 99, 8200 Aarhus N, Denmark; Department of Clinical Medicine, Health, Aarhus University, Palle Juul Jensens Boulevard 11, 8200 Aarhus N, Denmark.
Clin Chim Acta. 2025 Jan 15;565:119978. doi: 10.1016/j.cca.2024.119978. Epub 2024 Sep 26.
Wilson disease (WD) is a rare genetic disorder characterized by copper overload, primarily affecting the liver and brain, and the organ damage is believed to be caused by non-ceruloplasmin-bound copper (NCC). Accurate and early diagnosis is important for prognosis. Recently, a method for the measurement of NCC, exchangeable serum copper (CuEXC), was developed and shown to be a promising marker of WD, especially as the fraction of total copper, relative exchangeable copper (REC). This study aimed to validate the CuEXC extraction method and establish reference intervals for CuEXC and REC, as well as to examine short- and long-term stability of CuEXC in serum samples. The adult reference interval for CuEXC was 0.61-1.62 µmol/L and for REC 3.0-9.7 % based on 120 blood donors. Based on 88 children, the reference intervals for CuEXC was 0.45-1.16 µmol/L. The intervals for REC were 1.8-5.8 % for children <10 years and 2.3-8.5 % for children ≥10 years. Regarding stability, CuEXC increased following a logarithmic scale in uncentrifuged serum and exceeded the permissible difference of 10 % after 4 h. With long-term freezing at -20 °C, CuEXC was stable for 1.7 months. In conclusion, reference intervals for CuEXC and REC were established and confirmed to be substantially lower in children. Accurate reference intervals are important to ensure timely diagnosis of WD. Finally, our findings on stability have important implications and highlight the need for standardization of the pre-analytical handling of CuEXC samples in order to obtain comparable results within and between laboratories both for clinical and research use.
威尔逊病（WD）是一种罕见的遗传性疾病，其特征是铜过载，主要影响肝脏和大脑，而器官损伤被认为是由非铜蓝蛋白结合铜（NCC）引起的。准确和早期诊断对预后很重要。最近，开发了一种测量 NCC（可交换血清铜（CuEXC）的方法，并且该方法被证明是 WD 的一个很有前途的标志物，尤其是作为总铜的分数，相对可交换铜（REC）。本研究旨在验证 CuEXC 提取方法，并建立 CuEXC 和 REC 的参考区间，以及考察 CuEXC 在血清样本中的短期和长期稳定性。120 名献血者的成人 CuEXC 参考区间为 0.61-1.62µmol/L，REC 为 3.0-9.7%。基于 88 名儿童，CuEXC 的参考区间为 0.45-1.16µmol/L。儿童的 REC 区间为 <10 岁儿童为 1.8-5.8%，≥10 岁儿童为 2.3-8.5%。关于稳定性，在未离心的血清中 CuEXC 按对数比例增加，并且在 4 小时后超过 10%的允许差异。在-20°C 长期冷冻下，CuEXC 稳定 1.7 个月。总之，建立了 CuEXC 和 REC 的参考区间，并且证实儿童的参考区间明显较低。准确的参考区间对于确保 WD 的及时诊断很重要。最后，我们关于稳定性的发现具有重要意义，并且强调需要标准化 CuEXC 样本的分析前处理，以便在临床和研究用途中在实验室内部和之间获得可比较的结果。
