Epidemiological, clinical, paraclinical and molecular study of a cohort of 102 patients affected with autosomal recessive progressive cerebellar ataxia from Alsace, Eastern France: implications for clinical management

Neurogenetics. 2010 Feb;11(1):1-12. doi: 10.1007/s10048-009-0196-y. Epub 2009 May 14.


While Friedreich's ataxia (FRDA) and ataxia telangiectasia (AT) are known to be the two most frequent forms of autosomal recessive cerebellar ataxia (ARCA), knowledge on the other forms of ARCA has been obtained only recently, and they appear to be rarer. Little is known about the epidemiological features and the relative frequency of the ARCAs and only few data are available about the comparative features of ARCAs. We prospectively studied 102 suspected ARCA cases from Eastern France (including 95 from the Alsace region) between 2002 and 2008. The diagnostic procedure was based on a sequential strategic scheme. We examined the clinical, paraclinical and molecular features of the large cohort of patients and compared features and epidemiology according to molecular diagnosis. A molecular diagnosis could be established for 57 patients; 36 were affected with FRDA, seven with ataxia plus oculomotor apraxia type 2 (AOA2), four with AT, three with ataxia plus oculomotor apraxia type 1 (AOA1), three with Marinesco-Sjögren syndrome, two with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), one with ataxia with vitamin E deficiency (AVED) and one with autosomal recessive cerebellar ataxia type 2 (ARCA2). The group of patients with no identified mutation had a significantly lower spinocerebellar degeneration functional score corrected for disease duration (SDFS/DD ratio; p = 0.002) and comprised a significantly higher proportion of cases with onset after 20 years (p < 0.01). Extensor plantar reflexes were rarer and cerebellar atrophy was more frequent in the group of patients with a known non-Friedreich ARCA compared to all other patients (p < 0.0001 and p = 0.0003, respectively). Lower limb areflexia and electroneuromyographic evidences of peripheral neuropathy were more frequent in the Friedreich ataxia group than in the group with a known non-Friedreich ataxia and were more frequent in the later group than in the group with no identified mutation (p = 0.0001 and p = 0.01, respectively). The overall prevalence of ARCA in Alsace is 1/19,000. We can infer the prevalence of FRDA in Alsace to be 1/50,000 and infer that AT is approximately eight times less frequent than FRDA. MSS, AOA2 and ARSACS appear only slightly less frequent than AT. Despite the broad variability of severity, Friedreich ataxia patients are clinically distinct from the other forms of ARCA. Patients with no identified mutation have more often a pure cerebellar degenerative disease or a spastic ataxia phenotype. It appears that ARCA cases can be divided into two major groups of different prognosis, an early-onset group with a highly probable genetic cause and an adult-onset group with better prognosis for which a genetic cause is more difficult to prove but not excluded. ARCAs are rare, early-disabling and genetically heterogeneous diseases dominated by FRDA. Several of the recently identified ARCAs, such as AVED, ARSACS, AOA1, AOA2 and MSS, have a prevalence close to AT and should be searched for extensively irrespective of ethnic origins. The strategic scheme is a useful tool for the diagnosis of ARCAs in clinical practice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Brain / pathology
  • Cerebellar Ataxia / epidemiology
  • Cerebellar Ataxia / genetics*
  • Cerebellar Ataxia / therapy
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • France
  • Genes, Recessive
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Mutation
  • Myography / methods
  • Prospective Studies