Identification of Cerebrotendinous Xanthomatosis in High-Risk Children Using a Suspicion Index–Based Screening Strategy

Background Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid storage disorder that is amenable to disease-modifying therapy if diagnosed early. However, phenotypic heterogeneity frequently leads to delayed recognition, particularly in childhood. Methods We retrospectively screened pediatric patients with neurological and multisystem involvement using the Mignarri Suspicion Index (MI). Patients with MI ≥ 100 underwent biochemical and/or molecular evaluation for CTX. Results Of 65 high-risk children, CTX was confirmed in 3 (4.6%). All diagnosed patients had MI scores ≥ 100, but none exhibited the full classical triad. Median diagnostic delay was 7 years. Early initiation of chenodeoxycholic acid therapy led to biochemical normalization and clinical stabilization. Conclusions A suspicion index–based approach effectively identifies CTX among high-risk pediatric populations. Integrating MI screening with confirmatory testing may improve diagnostic pathways for rare but treatable neurometabolic disorders and reduce preventable morbidity.