A recent study published in the Journal of Inherited Metabolic Disease has demonstrated that exchangeable copper (ExchCo) and the ratio of exchangeable copper (REC) are potential serum biomarkers that can be used as complementary tests to ensure Wilson disease (WD) diagnosis and copper homeostasis within time.
The study found that REC and exchangeable copper were significantly higher in patients with WD than in the healthy controls and reduced considerably among the patients with WD compliant with the prescribed medication (dichotomized as poor or adequate).
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In the present study, the research team assessed the potential of ExchCo/REC in a well-characterized, real-world, multicentric cohort of patients with WD. The team included patients with a confirmed WD diagnosis from 3 in Barcelona. Serum samples were collected and analyzed for each patient. The patients were divided into 2 groups: the recent diagnosis group (n=7) and the treated WD group (n=41). Additionally, a control group with 56 nonWD individuals was included in the study.
For analysis, ExchCo and REC were measured in all the patients through inductively coupled plasma-mass-spectrometry. Furthermore, laboratory, demographic, and clinical data were collected for included patients. Using Chi-Squared, both groups were compared, and ExchCo/REC accuracy points, including sensitivity, specificity, and positive and negative predictive values, were evaluated for all patients.
According to study results, REC was significantly higher among the patients with WD than the controls. It was useful for identifying WD using the previously established cutoffs. Moreover, 44 (91.6%) patients with WD were detected by the specified diagnostic REC cutoffs, while only 4 patients of the cohort showed discordant levels. Furthermore, it was observed that REC values were below 15% in all control patients. Similarly, ExchCo was reported to be significantly higher in patients with WD compared to the controls and found to be reduced among patients with WD who were compliant with medication.
“To the best of our knowledge, only one recent paper performed in 36 WD children has shown the potential use of exchangeable copper to monitor therapy within the first 5 years of diagnosis”, the authors concluded.
WD is a rare genetic and recessive disorder of copper metabolism. It is caused by alterations in the ATP7B gene, which encodes the copper-transporting ATPase 2 enzyme, thereby leading to excessive copper deposition. Diagnosis of WD is often complex and well-established biomarkers such as ceruloplasmin and urinary copper show frequent positive/negative false results.
Exchangeable copper and REC have been shown as useful biomarkers of copper metabolism in different clinical cases of WD, with REC being more reliable for WD diagnosis, with a cutoff of ≥18.5% for new cases. However, these biomarkers have not been validated yet, nor have they been included in the current international guidelines for WD, which might be partially related to the presence of limited studies and lack of real-world experiences.
Reference
Mariño Z, Molera‐Busoms C, Badenas C, et al. Benefits of using exchangeable copper and the ratio of exchangeable copper in a real‐world cohort of patients with Wilson disease. Journal of Inherited Metabolic Disease. Published online May 30, 2023. doi:10.1002/jimd.12639
