Hereditary and Non-hereditary Cerebellar Ataxias in Latvia: Six Years of Experience at the National Reference Centre (ERN-RND Affiliated Partner)

Cerebellar ataxias are rare but disabling disorders, with marked regional differences in genetic subtypes. Data from Eastern Europe, especially the Baltic region, remain scarce. To describe the aetiological spectrum and diagnostic challenges of cerebellar ataxia in Latvia over a six-year period. A retrospective descriptive single centre study was conducted at the national reference centre for rare neurological disorders in Latvia. Patients diagnosed with cerebellar ataxia between 2019 and 2025 were reviewed. Clinical data, laboratory, imaging, and genetic testing were analysed. Of 116 patients, 37 underwent local repeat-expansion analysis (ATXN1/SCA1, ATXN2/SCA2, ATXN3/SCA3, CACNA1A/SCA6); 14 underwent NGS-based broad panels; and 9 were referred for RFC1 repeat-expansion analysis at an external European reference laboratory. Of 116 patients, 70 (60.3%) received a confirmed aetiological diagnosis. Non-hereditary ataxias were the largest subgroup (65.7% of confirmed), with immune-mediated ataxias (21.4%) and sporadic neurodegenerative MSA-C (20.0%) among the most frequent diagnoses. The genetic diagnostic yield was 20.7% (24/116). Among hereditary cases, autosomal dominant ataxias predominated with SCA2 as the most frequent subtype - contrasting with the SCA3 predominance reported in most European cohorts. Autosomal recessive ataxias accounted for 8.6%, with RFC1-related CANVAS identified in 5.7% of confirmed cases; notably, all four RFC1-CANVAS patients presented with focal cervical dystonia (p = 0.020). No cases of Friedreich's ataxia were confirmed, partly reflecting the absence of routine GAA repeat-expansion testing. The remaining 46 patients were classified as cerebellar ataxia of undetermined aetiology, largely due to limited access to comprehensive genetic testing. This is the first systematic study of cerebellar ataxia in Latvia. Regional variation in genetic subtypes, frequent RFC1-related dystonia, and limited access to comprehensive genetic testing highlight the need for expanded diagnostic capacity. These findings have implications for diagnosis, counselling, and emerging targeted therapies.