Clinical Determinants and Prognostic Impact of Delayed Diagnosis in Wilson's Disease

Background: Wilson's disease (WD) is a rare hereditary disorder caused by pathological copper accumulation in multiple tissues. We aimed to assess the extent and determinants of diagnostic delay in WD adult patients treated at a Polish referral center and its impact on prognosis. Methods: We retrospectively analyzed 268 patients with WD diagnosed between 2008 and 2023. The duration of diagnostic delay was assessed in relation to sex, age, initial and diagnostic symptoms, liver enzyme levels, the aspartate aminotransferase-to-platelet ratio index, severity of hepatic and neurological manifestations, functional dependence, and family history of WD. Clinical outcomes included survival, liver transplantation, and neurological deterioration. Results: The mean diagnostic delay was 22.5 months (standard deviation (SD) 27.9). The shortest delay occurred in patients with hepatic presentation (18.3 months, SD 23.6), followed by neurological (26.8 months, SD 28.6), and psychiatric symptoms (65 months, SD 52.3). Longer delay correlated with older age at diagnosis and higher prevalence of neurological symptoms. In univariate analysis, diagnostic delay significantly increased the risk of neurological deterioration (p = 0.02). Patients with neurological or psychiatric symptoms, severe liver damage, and late-onset disease were at higher risk for adverse outcomes. Conclusions: Diagnostic delay was not associated with mortality or the composite endpoint but was linked to neurological deterioration. Surrogate markers suggested a possible relationship between delay and disease advancement. The absence of a clear association with prognosis may reflect challenges in adjusting for confounding factors such as treatment adherence.