Clinical Characteristics of Spinocerebellar Ataxia Type 3 in Uruguay

Spinocerebellar ataxias (SCAs) are autosomal dominant genetic disorders characterized by progressive cerebellar degeneration and phenotypic variability. MJD/SCA3, the most prevalent form around the world and in Latin America, is also likely the most common hereditary ataxia in Uruguay. Despite its relevance, Uruguay lacks comprehensive epidemiological studies, and molecular diagnostics remain inaccessible in public health systems. This review provides a phenotypic description on genetically confirmed patients with MJD/SCA3 as a first step towards generating knowledge on this matter in our country. A retrospective review of 37 Uruguayan patients with suspected SCA was conducted. Sixteen patients with confirmed molecular diagnosis of MJD/SCA3 were included on this review. Data collected encompassed demographic information, genetic testing results, clinical manifestations, and imaging findings. Patients were evaluated at the Ataxias Polyclinic, Hospital de Cl & iacute;nicas, between 2019 and 2024 by the authors. Statistical analyses were performed using SPSS version 29.0. The mean age of symptom onset was 41.75 years, with gait ataxia as the initial symptom in 87.5% of cases. Clinical findings included appendicular ataxia (100%), dysarthria (90%), and oculomotor alterations (90%), with diverse deep sensitivity impairment in 62.5%. Genetic testing revealed an average of 72.9 CAG repeats in the ATXN3 gene. Cerebellar atrophy was observed in 75% of patients with MRI. Most had a diagnostic delay of 6.5 years and an autosomal dominant family history. Findings align with international descriptions of MJD/SCA3 while highlighting regional characteristics, including a potential genetic link with southern Brazil. The absence of dysautonomia, typically prevalent in MJD/SCA3, suggests underdiagnosis or insufficient evaluation. This study underscores the need for systematic clinical and molecular evaluations in Uruguay and serves as a foundation to understand hereditary ataxias at a national level. Further research is essential for improving diagnosis and management of this complex pathology.