The Case of Spinocerebellar Ataxias in Amazonas (Northern Brazil): An Analysis of Disease Frequency from a Geographic, Historical, and Genetic-Evolutionary Perspective.

The Spinocerebellar Ataxias (SCAs) are a group of hereditary neurodegenerative diseases that show a variable distribution among distinct ethnicities and geographic regions. In Brazil, a large and highly admixed country, the prevalence of SCAs has been investigated mostly in limited areas. Here we characterized the frequencies of SCA types in the state of Amazonas, as well as the geographic origin of SCA families, and compared them to the literature data available about the frequency of SCAs in other Brazilian regions. Patients were recruited at two referral centers for ataxias at Manaus/Amazonas. An active search of patients based on the local medical records and contacts from other institutions was also performed. The participants were genetically tested for expansions at ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7 and ATXN10. Overall, the number of positive SCA cases was low in this population (N = 18). Also, the most frequent type among SCA families was SCA2 (30%), followed by SCA3 (15%), SCA7 (15%) and SCA10 (one case). These results contrast with those of other Brazilian populations, where SCA3 is predominant over the other types, comprising more than 50% of cases. We concluded that the geographic isolation and the unique population history of Amazonas, including strong Amerindian ancestry and recent demographic growth, have led to a higher frequency of an SCA with multiple mutation origins (SCA2) instead of a SCA spread by European migration of ancestral mutations (SCA3). We suggest that considering these factors is crucial for a better understanding of the epidemiology of hereditary diseases.