Clinical and genetic characteristics of sporadic adult-onset degenerative ataxia

Ilaria Giordano, Florian Harmuth, Heike Jacobi, Brigitte Paap, Stefan Vielhaber, Judith Machts, Ludger Schöls, Matthis Synofzik, Marc Sturm, Chantal Tallaksen, Iselin M Wedding, Sylvia Boesch, Andreas Eigentler, Bart van de Warrenburg, Judith van Gaalen, Christoph Kamm, Ales Dudesek, Jun-Suk Kang, Dagmar Timmann, Gabriella SilvestriMarcella Masciullo, Thomas Klopstock, Christiane Neuhofer, Christos Ganos, Alessandro Filla, Peter Bauer, Sophie Tezenas du Montcel, Thomas Klockgether

Research output: Contribution to journalArticlepeer-review


OBJECTIVE: To define the clinical phenotype and natural history of sporadic adult-onset degenerative ataxia and to identify putative disease-causing mutations.

METHODS: The primary measure of disease severity was the Scale for the Assessment and Rating of Ataxia (SARA). DNA samples were screened for mutations using a high-coverage ataxia-specific gene panel in combination with next-generation sequencing.

RESULTS: The analysis was performed on 249 participants. Among them, 83 met diagnostic criteria of clinically probable multiple system atrophy cerebellar type (MSA-C) at baseline and another 12 during follow-up. Positive MSA-C criteria (4.94 ± 0.74, p < 0.0001) and disease duration (0.22 ± 0.06 per additional year, p = 0.0007) were associated with a higher SARA score. Forty-eight participants who did not fulfill MSA-C criteria and had a disease duration of >10 years were designated sporadic adult-onset ataxia of unknown etiology/non-MSA (SAOA/non-MSA). Compared with MSA-C, SAOA/non-MSA patients had lower SARA scores (13.6 ± 6.0 vs 16.0 ± 5.8, p = 0.0200) and a slower annual SARA increase (1.1 ± 2.3 vs 3.3 ± 3.2, p = 0.0013). In 11 of 194 tested participants (6%), a definitive or probable genetic diagnosis was made.

CONCLUSIONS: Our study provides quantitative data on the clinical phenotype and progression of sporadic ataxia with adult onset. Screening for causative mutations with a gene panel approach yielded a genetic diagnosis in 6% of the cohort.


Original languageEnglish
Pages (from-to)1043-1049
Number of pages7
Issue number10
Publication statusPublished - Sep 5 2017


  • Aged
  • Ataxia
  • DNA Mutational Analysis
  • Europe
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Neurodegenerative Diseases
  • Severity of Illness Index
  • Clinical Trial
  • Journal Article
  • Multicenter Study


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