title: Spinocerebellar ataxia type 3/Machado-Joseph disease starting before adolescence.
abstract: Onset of Machado-Joseph disease (SCA3/MJD) before adolescence has been rarely reported. This study aims to describe a cohort of SCA3/MJD with onset before 12 years of age, comparing their disease progression with the progression observed in patients with usual disease onset. We identified all cases from our cohort whose onset was before adolescence. After consent, patients were examined with clinical scales Scale for the Assessment and Rating of Ataxia (SARA) and Neurological Examination Score for Spinocerebellar Ataxia (NESSCA). Gender, age, age at onset, disease duration, CAG expanded repeats, transmitting parent, and anticipation of cases with infantile and adult onset were studied. Progression of NESSCA and SARA scores was estimated through a mixed model, and was compared with a historical group with onset after adolescence. Between 2000 and 2014, 461 symptomatic individuals from our region were diagnosed as SCA3/MJD. Onset of eight cases (2.2%), all heterozygotes, was before adolescence: seven were females (p = 0.054). CAG expanded repeats--75 ± 3 versus 84 ± 4--and anticipations--7 ± 9.7 versus 14.4 ± 7.2 years--were different between early childhood and adult onset groups (p < 0.03). The median survival of early childhood onset group was 23 years of age. The annual progression of SARA--2.3 and 0.6 points/year (p = 0.001)--and NESSCA--2.04 and 0.88 points/year (p = 0.043)--was faster in childhood than in adult onset group. Onset of SCA3/MJD before adolescence was related to larger expanded CAG repeats in heterozygosis; females seemed to be at higher risk. Disease progression was faster than in SCA3/MJD starting after 12 years.
authors.affiliation: Programa de Pós-Graduação na Saúde da Criança e do Adolescente, Universidade Federal do Rio Grande do Sul, Rio Grande do Sul, Brazil.|Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, 90.035-903, Porto Alegre, Brazil.
authors.forename: Karina Carvalho
authors.initials: KC
authors.lastname: Donis
authors.affiliation: Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, 90.035-903, Porto Alegre, Brazil.
authors.forename: Jonas Alex Morales
authors.initials: JA
authors.lastname: Saute
authors.affiliation: Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Rio Grande do Sul, Brazil.
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: Krum-Santos
authors.affiliation: Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Rio Grande do Sul, Brazil.|Laboratório de Identificação Genética, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Gabriel Vasata
authors.initials: GV
authors.lastname: Furtado
authors.affiliation: Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Rio Grande do Sul, Brazil.|Laboratório de Identificação Genética, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Eduardo Preusser
authors.initials: EP
authors.lastname: Mattos
authors.affiliation: Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, 90.035-903, Porto Alegre, Brazil.|Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Rio Grande do Sul, Brazil.|Laboratório de Identificação Genética, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.|Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Rio Grande do Sul, Brazil.|Instituto de Genética Médica Populacional (INAGEMP), Porto Alegre, Brazil.
authors.forename: Maria Luiza
authors.initials: ML
authors.lastname: Saraiva-Pereira
authors.affiliation: Departamento de Estatística, Universidade Federal do Rio Grande do Sul, Rio Grande do Sul, Brazil.
authors.forename: Vanessa Leotti
authors.initials: VL
authors.lastname: Torman
authors.affiliation: Programa de Pós-Graduação na Saúde da Criança e do Adolescente, Universidade Federal do Rio Grande do Sul, Rio Grande do Sul, Brazil. ljardim@hcpa.edu.br.|Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, 90.035-903, Porto Alegre, Brazil. ljardim@hcpa.edu.br.|Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Rio Grande do Sul, Brazil. ljardim@hcpa.edu.br.|Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Rio Grande do Sul, Brazil. ljardim@hcpa.edu.br.|Laboratório de Identificação Genética, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. ljardim@hcpa.edu.br.|Departamento de Medicina Interna, Universidade Federal do Rio Grande do Sul, Rio Grande do Sul, Brazil. ljardim@hcpa.edu.br.|Instituto de Genética Médica Populacional (INAGEMP), Porto Alegre, Brazil. ljardim@hcpa.edu.br.
authors.forename: Laura Bannach
authors.identifier: http://orcid.org/0000-0001-6907-5068
authors.initials: LB
authors.lastname: Jardim
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D017827:Machado-Joseph Disease / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D012720:Severity of Illness Index; D055815:Young Adult
keywords: Early childhood onset; Machado-Joseph disease; Natural history; Polyglutamine disorders; Spinocerebellar ataxia type 3