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Genetic Epidemiology and Clinical Characteristics of Patients with Spinocerebellar Ataxias in an Unexplored Brazilian State, Using Strategies for Resource-Limited Settings

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Abstract

Spinocerebellar ataxias (SCAs) have a worldwide average prevalence of 2.7 cases per 100,000 individuals, with significant geographic variability. This study aimed to develop resource-limited strategies to detect and characterize the frequency and genetic-clinical profile of SCAs in an unexplored population from Alagoas State, a low Human Development Index state in northeastern Brazil. Active search strategies were employed to identify individuals with a diagnosis or clinical suspicion of SCAs, and a protocol for clinical and molecular evaluation was applied in collaboration with a reference center in Neurogenetics. A total of 73 individuals with SCAs were identified, with a minimum estimated prevalence of 2.17 cases per 100,000 inhabitants. SCA3 was the most common type (75.3%), followed by SCA7 (15.1%), SCA1 (6.8%), and SCA2 (2.7%). Patients with SCA3 subphenotype 2 were the most predominant. Detailed analysis of patients with SCA3 and SCA7 revealed age at onset and clinical features congruent with other studies, with gait disturbance and reduced visual capacity in SCA7 as the main initial manifestations. The study also identified many asymptomatic individuals at risk of developing SCAs. These findings demonstrate that simple and collaborative strategies can enhance the detection capacity of rare diseases such as SCAs in resource-limited settings and that Alagoas State has a minimum estimated prevalence of SCAs similar to the world average.

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Authors and Affiliations

  1. Postgraduate Program, Department of Neurosciences and Behavioral Sciences, Ribeirão Preto Medical School, University of São Paulo, Campus Universitário - Rua Bernardino de Campos, 1000 - Centro, Ribeirão Preto, SP, 65470-000, Brazil

    Débora Beserra Vilar Moraes

  2. Graduation Course, Faculty of Medicine, Federal University of Alagoas, Campus Universitário, Avenida Lourival Melo Mota S/N, Tabuleiro dos Martins, CEP 57.072-900, Maceió, Alagoas, Brazil

    Tácio Luis Cavalcante Coradine & Everton Vieira Lopes Silva

  3. Division of Neurology, Faculty of Medicine, Federal University of Ceará, Rua Prof. Costa Mendes, 1408 – 4°, Andar, CEP: 60.430-140, Fortaleza, Brazil

    Manoel Alves Sobreira-Neto

  4. Department of Neurosciences and Behavioral Sciences, Ribeirão Preto Medical School, University of São Paulo, Campus Universitário - Rua Bernardino de Campos, 1000 - Centro, Ribeirão Preto, SP, 65470-000, Brazil

    Wilson Marques Jr & Vitor Tumas

  5. Division of Neurology, Faculty of Medicine, Federal University of Alagoas, Campus Universitário, Avenida Lourival Melo Mota S/N, Tabuleiro dos Martins, CEP 57.072-900, Maceió, Alagoas, Brazil

    Lívia Leite Góes Gitaí

  6. Maceió, Brazil

    Lívia Leite Góes Gitaí

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  1. Débora Beserra Vilar Moraes
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  2. Tácio Luis Cavalcante Coradine
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  3. Everton Vieira Lopes Silva
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  4. Manoel Alves Sobreira-Neto
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  5. Wilson Marques Jr
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  6. Lívia Leite Góes Gitaí
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  7. Vitor Tumas
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Contributions

All authors contributed to the study conception and design (Moraes DBV, Marques Jr W, Gitaí LLG, Tumas V); and/or the acquisition, analysis, or interpretation of data (Moraes DBV, Coradine TLC, Silva EVL, Marques Jr W, Gitaí LLG, Tumas V); and/or made substantial contributions in writing and reviewing the manuscript (Moraes DBV, Gitaí LLG, Sobreira-Neto MA, Tumas V).

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Correspondence to Lívia Leite Góes Gitaí or Vitor Tumas.

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The study was approved by the Institutional Ethics Committee of Federal University of Alagoas and all patients have signed written informed consent to participate and to publish prior to enrolment in the study.

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The authors declare no competing interests.

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ESM 1:

Table S1 Frequency of geographic distribution of SCA patients submitted to clinical evaluation. Figure S1: Correlation between the number of abnormal CAG repeats and age of onset in SCA3 and SCA7. Figure S2: Correlation between scores on severity assessment scales and duration of disease in SCA3 and SCA7.

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Moraes, D.B.V., Coradine, T.L.C., Silva, E.V.L. et al. Genetic Epidemiology and Clinical Characteristics of Patients with Spinocerebellar Ataxias in an Unexplored Brazilian State, Using Strategies for Resource-Limited Settings. Cerebellum 23, 609–619 (2024). https://doi.org/10.1007/s12311-023-01581-x

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