title: Delayed-onset Friedreich's ataxia revisited.
abstract: BACKGROUND
  Friedreich's ataxia usually occurs before the age of 25. Rare variants have been described, such as late-onset Friedreich's ataxia and very-late-onset Friedreich's ataxia, occurring after 25 and 40 years, respectively. We describe the clinical, functional, and molecular findings from a large series of late-onset Friedreich's ataxia and very-late-onset Friedreich's ataxia and compare them with typical-onset Friedreich's ataxia.
  
  
  METHODS
  Phenotypic and genotypic comparison of 44 late-onset Friedreich's ataxia, 30 very late-onset Friedreich's ataxia, and 180 typical Friedreich's ataxia was undertaken.
  
  
  RESULTS
  Delayed-onset Friedreich's ataxia (late-onset Friedreich's ataxia and very-late-onset Friedreich's ataxia) had less frequently dysarthria, abolished tendon reflexes, extensor plantar reflexes, weakness, amyotrophy, ganglionopathy, cerebellar atrophy, scoliosis, and cardiomyopathy than typical-onset Friedreich's ataxia, along with less severe functional disability and shorter GAA expansion on the smaller allele (P < 0.001). Delayed-onset Friedreich's ataxia had lower scale for the assessment and rating of ataxia and spinocerebellar degeneration functional scores and longer disease duration before wheelchair confinement (P < 0.001). Both GAA expansions were negatively correlated to age at disease onset (P < 0.001), but the smaller GAA expansion accounted for 62.9% of age at onset variation and the larger GAA expansion for 15.6%. In this comparative study of late-onset Friedreich's ataxia and very-late-onset Friedreich's ataxia, no differences between these phenotypes were demonstrated.
  
  
  CONCLUSIONS
  Typical- and delayed-onset Friedreich's ataxia are different and Friedreich's ataxia is heterogeneous. Late-onset Friedreich's ataxia and very-late-onset Friedreich's ataxia appear to belong to the same clinical and molecular continuum and should be considered together as "delayed-onset Friedreich's ataxia." As the most frequently inherited ataxia, Friedreich's ataxia should be considered facing compatible pictures, including atypical phenotypes (spastic ataxia, retained reflexes, lack of dysarthria, and lack of extraneurological signs), delayed disease onset (even after 60 years of age), and/or slow disease progression.
authors.affiliation: Département de Neurologie, Hôpital de Hautepierre, CHU de Strasbourg, Strasbourg, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Lecocq
authors.affiliation: Département de Génétique et Cytogénétique, Hôpital de la Pitié-Salpêtrière, AP-HP, Paris, France.
authors.forename: Perrine
authors.initials: P
authors.lastname: Charles
authors.affiliation: Département de Neurologie et Pathologie du mouvement, Hôpital de la Timone, Marseille, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Azulay
authors.affiliation: Université De Bordeaux, Institut des Maladies Neurodégénératives, CNRS UMR 5293, Bordeaux, France; and Département de Neurologie, Hôpital Pellegrin, CHU de Bordeaux, Bordeaux, France.
authors.forename: Wassilios
authors.initials: W
authors.lastname: Meissner
authors.affiliation: Laboratoire de Neurologie Expérimentale, Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors.forename: Myriam
authors.initials: M
authors.lastname: Rai
authors.affiliation: Département de Neurologie et Pathologie du mouvement, Hôpital de la Timone, Marseille, France.
authors.forename: Karine
authors.initials: K
authors.lastname: N'Guyen
authors.affiliation: Laboratoire d'Explorations Fonctionnelles, Centre de Référence Maladies Neuromusculaires Nantes-Angers, Hôtel-Dieu, CHU Nantes, Nantes, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Péréon
authors.affiliation: Département de Neurologie, Hôpital Purpan, CHU de Toulouse, Toulouse, France.
authors.forename: Nelly
authors.initials: N
authors.lastname: Fabre
authors.affiliation: Département de Neurologie et Pathologie du mouvement, Hôpital de la Timone, Marseille, France.
authors.forename: Elsa
authors.initials: E
authors.lastname: Robin
authors.affiliation: Département de Neurologie, Hôpital Emile-Muller, Mulhouse, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Courtois
authors.affiliation: Service de Neurophysiologie, Hôpital Charles-Nicolle, CHU de Rouen, Rouen, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Guyant-Maréchal
authors.affiliation: Département de Neurologie, CHU de Brest, Brest, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Zagnoli
authors.affiliation: Département de Neurologie, Hôpital de Hautepierre, CHU de Strasbourg, Strasbourg, France.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Rudolf
authors.affiliation: Département de Neurologie, Hôpital de Hautepierre, CHU de Strasbourg, Strasbourg, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Renaud
authors.affiliation: Département de Neurologie, Hôpital GR Laënnec, CHU de Nantes, Nantes, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Sévin-Allouet
authors.affiliation: UPMC Université Paris 06, UMR_S975, Centre de Recherche Institut du Cerveau et de la Moelle, CNRS 7225, Hôpital de la Pitié-Salpêtrière, Paris, France; and INSERM, UMR_S975, Paris, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Lesne
authors.affiliation: Laboratoire de Neurologie Expérimentale, Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors.forename: Nick
authors.initials: N
authors.lastname: Alaerts
authors.affiliation: CHU Bordeaux, Service de Génétique Médicale, Université Bordeaux, Laboratoire Maladies Rares: Génétique et Métabolisme (MRGM), EA4576, Bordeaux, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Goizet
authors.affiliation: Département de Neurologie, Hôpital Purpan, CHU de Toulouse, Toulouse, France; and Service de Génétique Médicale, Hôpital Purpan, CHU de Toulouse, Toulouse, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Calvas
authors.affiliation: Département de Neurologie et Pathologie du mouvement, Hôpital de la Timone, Marseille, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Eusebio
authors.affiliation: Laboratoire de Génétique Moléculaire, Institut Universitaire de Recherche Clinique, Université de Montpellier, CHU Montpellier, Montpellier, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Guissart
authors.affiliation: Département de Neurologie, Hôpital GR Laënnec, CHU de Nantes, Nantes, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Derkinderen
authors.affiliation: Université De Bordeaux, Institut des Maladies Neurodégénératives, CNRS UMR 5293, Bordeaux, France; and Département de Neurologie, Hôpital Pellegrin, CHU de Bordeaux, Bordeaux, France.
authors.forename: Francois
authors.initials: F
authors.lastname: Tison
authors.affiliation: Département de Génétique et Cytogénétique, Hôpital de la Pitié-Salpêtrière, AP-HP, Paris, France; UPMC Université Paris 06, UMR_S975, Centre de Recherche Institut du Cerveau et de la Moelle, CNRS 7225, Hôpital de la Pitié-Salpêtrière, Paris, France; and INSERM, UMR_S975, Paris, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
authors.affiliation: Laboratoire de Génétique Moléculaire, Institut Universitaire de Recherche Clinique, Université de Montpellier, CHU Montpellier, France; and Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM-U964/CNRS-UMR7104/Université de Strasbourg, Illkirch, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Koenig
authors.affiliation: Laboratoire de Neurologie Expérimentale, Université Libre de Bruxelles (ULB), Brussels, Belgium; and Département de Neurologie, Hôpital Erasme, Brussels, Belgium.
authors.forename: Massimo
authors.initials: M
authors.lastname: Pandolfo
authors.affiliation: Département de Neurologie, Hôpital de Hautepierre, CHU de Strasbourg, Strasbourg, France; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM-U964/CNRS-UMR7104/Université de Strasbourg, Illkirch, France; and Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Tranchant
authors.affiliation: Département de Génétique et Cytogénétique, Hôpital de la Pitié-Salpêtrière, AP-HP, Paris, France; UPMC Université Paris 06, UMR_S975, Centre de Recherche Institut du Cerveau et de la Moelle, CNRS 7225, Hôpital de la Pitié-Salpêtrière, Paris, France; and INSERM, UMR_S975, Paris, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Dürr
authors.affiliation: Département de Neurologie, Hôpital de Hautepierre, CHU de Strasbourg, France Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM-U964/CNRS-UMR7104/Université de Strasbourg, Illkirch, France; and Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Anheim
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D009202:Cardiomyopathies / Q000175:diagnosis / Q000209:etiology; D002648:Child; D004562:Electrocardiography; D005260:Female; D005621:Friedreich Ataxia / Q000097:blood / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D005838:Genotype; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007391:International Cooperation; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012189:Retrospective Studies; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D018911:Trinucleotide Repeats / Q000235:genetics*; D055815:Young Adult
chemical_list: D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human
keywords: Friedreich's ataxia; corticospinal tract; genetics; imaging; peripheral neuropathy