title: Nonneurological Involvement in Late-Onset Friedreich Ataxia (LOFA): Exploring the Phenotypes.
abstract: Friedreich's ataxia (FDRA) is the most common inherited ataxia worldwide, caused by homozygous GAA expansions in the FXN gene. Patients usually have early onset ataxia, areflexia, Babinski sign, scoliosis and pes cavus, but at least 25 % of cases have atypical phenotypes. Disease begins after the age of 25 in occasional patients (late-onset Friedreich ataxia (LOFA)). Little is known about the frequency and clinical profile of LOFA patients. One hundred six patients with molecular confirmation of FDRA and followed in three Brazilian outpatient centers were enrolled. General demographics, GAA expansion size, age at onset, cardiac, endocrine, and skeletal manifestations were evaluated and compared between LOFA and classic FDRA (cFDRA) groups. We used Mann-Whitney and Fisher tests to compare means and proportions between groups; p values <0.05 were considered significant. LOFA accounted for 17 % (18/106) and cFDRA for 83 % (88/106) of the patients. There were 13 and 48 women in each group, respectively. LOFA patients were significantly older and had smaller GAA expansions. Clinically, LOFA group had a tendency toward lower frequency of diabetes/impaired glucose tolerance (5.8 vs. 17 %, p = 0.29) and cardiomyopathy (16.6 vs. 28.4 %, p = 0.38). Skeletal abnormalities were significantly less frequent in LOFA (scoliosis 22 vs. 61 %, p = 0.003, and pes cavus 22 vs.75 %, p < 0.001) as were spasticity and sustained reflexes, found in 22 % of LOFA patients but in none of the cFDRA patients (p = 0.001). LOFA accounts for 17 % of Brazilian FDRA patients evaluated herein. Clinically, orthopedic features and spasticity with retained reflexes are helpful tips to differentiate LOFA from cFDRA patients.
authors.affiliation: Department of Neurology, University of Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, Cidade Universitaria "Zeferino Vaz", Campinas, SP, Brazil, ZiP Code 13083-970.
authors.forename: Alberto R M
authors.initials: AR
authors.lastname: Martinez
authors.affiliation: Movement Disorders Unit, Neurology Service, Internal Medicine Department, Hospital de Clínicas, Federal University of Paraná, Curitiba, Brazil.
authors.forename: Adriana
authors.initials: A
authors.lastname: Moro
authors.affiliation: Division of General Neurology and Ataxia Unit, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Agessandro
authors.initials: A
authors.lastname: Abrahao
authors.affiliation: Department of Neurology, University of Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, Cidade Universitaria "Zeferino Vaz", Campinas, SP, Brazil, ZiP Code 13083-970.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Faber
authors.affiliation: Movement Disorders Unit, Neurology Service, Internal Medicine Department, Hospital de Clínicas, Federal University of Paraná, Curitiba, Brazil.
authors.forename: Conrado R
authors.initials: CR
authors.lastname: Borges
authors.affiliation: Department of Neurology, University of Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, Cidade Universitaria "Zeferino Vaz", Campinas, SP, Brazil, ZiP Code 13083-970.
authors.forename: Thiago J R
authors.initials: TJ
authors.lastname: Rezende
authors.affiliation: Department of Neurology, University of Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, Cidade Universitaria "Zeferino Vaz", Campinas, SP, Brazil, ZiP Code 13083-970.
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Martins
authors.affiliation: Movement Disorders Unit, Neurology Service, Internal Medicine Department, Hospital de Clínicas, Federal University of Paraná, Curitiba, Brazil.
authors.forename: Mariana
authors.initials: M
authors.lastname: Moscovich
authors.affiliation: University of Toronto, Toronto, Canada.
authors.forename: Renato P
authors.initials: RP
authors.lastname: Munhoz
authors.affiliation: Medical Genetics Service - HCPA, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
authors.forename: Sandra Leistner
authors.initials: SL
authors.lastname: Segal
authors.affiliation: Movement Disorders Unit, Neurology Service, Internal Medicine Department, Hospital de Clínicas, Federal University of Paraná, Curitiba, Brazil.
authors.forename: Walter O
authors.initials: WO
authors.lastname: Arruda
authors.affiliation: Medical Genetics Service - HCPA, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
authors.forename: Maria Luiza
authors.initials: ML
authors.lastname: Saraiva-Pereira
authors.affiliation: Movement Disorders Unit, Neurology Service, Internal Medicine Department, Hospital de Clínicas, Federal University of Paraná, Curitiba, Brazil.
authors.forename: Simone
authors.initials: S
authors.lastname: Karuta
authors.affiliation: Division of General Neurology and Ataxia Unit, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: José Luiz
authors.initials: JL
authors.lastname: Pedroso
authors.affiliation: Department of Neurology, University of Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, Cidade Universitaria "Zeferino Vaz", Campinas, SP, Brazil, ZiP Code 13083-970.
authors.forename: Anelyssa
authors.initials: A
authors.lastname: D'Abreu
authors.affiliation: Medical Genetics Service - HCPA, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
authors.forename: Laura B
authors.initials: LB
authors.lastname: Jardim
authors.affiliation: Department of Medical Genetics, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Íscia
authors.initials: Í
authors.lastname: Lopes-Cendes
authors.affiliation: Division of General Neurology and Ataxia Unit, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Orlando G
authors.initials: OG
authors.lastname: Barsottini
authors.affiliation: Movement Disorders Unit, Neurology Service, Internal Medicine Department, Hospital de Clínicas, Federal University of Paraná, Curitiba, Brazil.
authors.forename: Hélio A G
authors.initials: HA
authors.lastname: Teive
authors.affiliation: Department of Neurology, University of Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, Cidade Universitaria "Zeferino Vaz", Campinas, SP, Brazil, ZiP Code 13083-970. mcfrancajr@uol.com.br.
authors.forename: Marcondes C
authors.initials: MC
authors.lastname: França
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D005260:Female; D005621:Friedreich Ataxia / Q000503:physiopathology*; D006801:Humans; D008297:Male; D010641:Phenotype
keywords: Ataxia; Late-onset Friedreich ataxia; Retained reflexes; Spastic ataxia