Serum Neurofilament Light Levels in Patients with Cerebrotendinous Xanthomatosis: a Pilot Study

Introduction: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder caused by pathogenic variants in CYP27A1, leading to cholestanol accumulation and progressive neurological dysfunction. Neurofilament light chain (NfL) is a biomarker of neuroaxonal injury in several hereditary ataxias, but its role in CTX has not been investigated. We aimed to determine whether serum NfL is elevated in CTX and whether it correlates with clinical severity. Methods: Five genetically confirmed CTX patients and five age-, sex-, and body mass index–matched healthy controls were evaluated. Clinical severity was assessed using the Scale for the Assessment and Rating of Ataxia (SARA). Serum NfL concentrations were measured using single-molecule array technology. Group comparisons were performed using the Mann–Whitney U test, and associations were assessed using Spearman’s correlation coefficient. Results: Serum NfL levels were significantly higher in CTX patients than in controls (median 14.63 pg/mL [interquartile range 5.10–18.17] vs. 2.90 pg/mL [2.52–3.56]; p = 0.008). Within the CTX group, NfL levels showed a strong positive correlation with SARA scores (Spearman's ρ = 0.90, p = 0.037), indicating higher NfL levels in patients with greater neurological impairment. Conclusion: Serum NfL is elevated in CTX and correlates with ataxia severity, supporting its potential relevance as a marker of neuroaxonal injury in this disorder. Larger longitudinal studies are needed to confirm these preliminary findings and clarify the role of NfL in disease monitoring.