Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2025 Jun 4;24(4):108.
doi: 10.1007/s12311-025-01854-7.

Machado-Joseph disease in Brazil and other South American countries: A systematic Review and Meta-analysis of Prevalence, CAG Repeat Lengths, Age At Onset, and Ancestry

Lucas Schenatto Sena  1   2 , Leonardo Simão Medeiros  2   3 , Laura Bannach Jardim  4   5   6
Affiliations
Meta-Analysis

Machado-Joseph disease in Brazil and other South American countries: A systematic Review and Meta-analysis of Prevalence, CAG Repeat Lengths, Age At Onset, and Ancestry

Lucas Schenatto Sena et al. Cerebellum. .

Abstract

Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is a CAG expansion (CAGexp) disease whose genetic characteristics in South America (SA) are not well known. Our aim was to perform a systematic review and meta-analysis on the subject. Number of SA cases, ages at onset (AO), normal CAG repeats (CAGnormal) and CAGexp, and haplotypes, were searched in Pubmed, Embase, Lilacs, SciELO, ProQuest™ Dissertations & Theses Citation Index, BDTD and La Referencia by a PROSPERO registered protocol. Quantitative data were meta analysed. 26 non-replicated papers and dissertations out of 713 publications were included. 2,111 SCA3/MJD patients were reported, 16 living in Argentina, 10 in Chile, 41 in Venezuela, 18 in Peru, and 2,026 in Brazil between 2011 and 2024. Four individual-participant data (IPD) were obtained. The mean (95% CI; sample size) of CAGnormal, CAGexp and AO were 21.90 (21.53-22.27; 802) and 74.65 (74.43-74.87; 1,100) repeats, and 34.90 (34.25-35.31; 1,102) years. CAGexp explained 62% of the AO variability in IPD (789). The CAGexp effects over AO varied according to geographical origin, impacting in the models to predict AO. It was similar in three Brazilian cohorts, while among Peruvians the AO seemed to be earlier than expected by their CAGexp legths. Three studies found the rs1048755-rs12895357-rs7158733 haplotypes ACA, CCG and AGA in Brazilian patients. In conclusion, current evidence supports the relationship between SCA3/MJD and Portuguese-Azoreans, while the different CAGexp effects on AO across SA populations need to be studied to determine the underlying modifying factors.

Keywords: Age at onset; CAG repeat length; Genetic modulator; Machado-Joseph disease; Phenotypic modifier; Spinocerebellar ataxia type 3; Trait biomarker.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics Approval: This systematic review was part of a study on SCA3/MJD approved by the Ethics Committee of our institution (Comitê de Ética em Pesquisa do Hospital de Clínicas de Porto Alegre) under the id CAAE 95633218.2.0000.5327. The methods followed the Preferred Reporting Items for Systematic Reviews and Metaanalysis guidelines (PRISMA) ( https://www.equator-network.org/reporting-guidelines/prisma/ ). No consent form was applied. Conflicts of interest: The authors declare no competing interests.

References

    1. Klockgether T, Mariotti C, Paulson HL. Spinocerebellar ataxia. Nat Rev Dis Primers. 2019;5(1):24. https://doi.org/10.1038/s41572-019-0074-3 . - DOI - PubMed
    1. Ruano L, Melo C, Silva MC, Coutinho P. The global epidemiology of hereditary ataxia and spastic paraplegia: a systematic review of prevalence studies. Neuroepidemiology. 2014;42(3):174–83. https://doi.org/10.1159/000358801 . - DOI - PubMed
    1. Galecio-Castillo M, Gutierrez-Arratia J, Abad-Murillo A, Sarapura-Castro E, Araujo-Aliaga I, Saldarriaga-Mayo A, et al. Epidemiology of autosomal dominant spinocerebellar ataxias in Latin America: A systematic review and meta-analysis. Cerebellum. 2025;24(3):75. https://doi.org/10.1007/s12311-025-01826-x . - DOI - PubMed
    1. Saute JAM, Jardim LB. Machado Joseph disease: clinical and genetic aspects, and current treatment. Expert Opin Orphan Drugs. 2015;3(5):517–35. https://doi.org/10.1517/21678707.2015.1025747 . - DOI
    1. de Mattos EP, Kolbe Musskopf M, Bielefeldt Leotti V, Saraiva-Pereira ML, Jardim LB. Genetic risk factors for modulation of age at onset in Machado-Joseph disease/spinocerebellar ataxia type 3: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2019;90(2):203–10. https://doi.org/10.1136/jnnp-2018-319200 . - DOI - PubMed

LinkOut - more resources