Autosomal Recessive Ataxias in Northeast Brazil: A Regional Multicenter Case Series.

Abstract

Hereditary cerebellar ataxias are a diverse group of neurodegenerative disorders characterized by progressive cerebellar dysfunction and possible multisystemic involvement. While significant advancements have been made in understanding autosomal dominant cerebellar ataxias (ADCAs), autosomal recessive cerebellar ataxias (ARCAs) remain less extensively investigated than autosomal dominant ataxias, particularly in regions with high consanguinity. This study aimed to characterize 57 patients with ARCAs in Ceará, northeast Brazil. We analyzed 57 patients diagnosed with ARCAs caused by biallelic variants in ARCA-associated genes. Patients underwent clinical evaluations, including neurological examinations and functional assessments.

Results: Friedreich's ataxia (FRDA) was the most prevalent diagnosis, accounting for 12 cases (21%), followed by Ataxia-Telangiectasia (A-T) with (N = 9; 15.8%) and Niemann-Pick Disease Type C (NPC) (N = 9; 15.8%). Metabolic disorders, including Cerebrotendinous Xanthomatosis (N = 6;10.5%) were also common causes. The cohort demonstrated a broad age distribution, with childhood-onset conditions such as A-T predominantly affecting younger patients. In contrast, adult-onset conditions like FRDA and NPC were more common in those aged 18 years and older.

Discussion: This study highlights the heterogeneity of ARCAs in a region with high consanguinity, reflecting these disorders' diverse genetic and clinical spectrum.

Conclusion: The clinical and genetic characterization of ARCAs presented in this case series emphasizes the importance of early diagnosis, genetic confirmation, and targeted management strategies. Our findings highlight the need for continued research and expanded diagnostic programs, particularly in regions with high consanguinity, to improve patient outcomes and advance therapeutic development.