Diagnosis and treatment of Friedreich ataxia: a European perspective

Nat Rev Neurol. 2009 Apr;5(4):222-34. doi: 10.1038/nrneurol.2009.26.

Abstract

Friedreich ataxia is the most frequent hereditary ataxia, with an estimated prevalence of 3-4 cases per 100,000 individuals. This autosomal-recessive neurodegenerative disease is characterized by progressive gait and limb ataxia, dysarthria, lower-limb areflexia, decreased vibration sense, muscular weakness in the legs, and a positive extensor plantar response. Non-neurological signs include hypertrophic cardiomyopathy and diabetes mellitus. Symptom onset typically occurs around puberty, and life expectancy is 40-50 years. Friedreich ataxia is usually caused by a large GAA-triplet-repeat expansion within the first intron of the frataxin (FXN) gene. FXN mutations cause deficiencies of the iron-sulfur cluster-containing subunits of the mitochondrial electron transport complexes I, II, and III, and of the iron-sulfur protein aconitase. Mitochondrial dysfunction has been addressed in several open-label, non-placebo-controlled trials, which indicated that treatment with idebenone might ameliorate hypertrophic cardiomyopathy; a well-designed phase II trial suggested concentration-dependent functional improvements in non-wheelchair-bound children and adolescents. Other current experimental approaches address iron-mediated toxicity, or aim to increase FXN expression through the use of erythropoietin and histone deacetylase inhibitors. This Review provides guidelines, from a European perspective, for the diagnosis of Friedreich ataxia, differential diagnosis of ataxias and genetic counseling, and treatment of neurological and non-neurological symptoms.

Publication types

  • Review

MeSH terms

  • Antioxidants / therapeutic use
  • Diagnosis, Differential
  • Diagnostic Imaging
  • Europe / epidemiology
  • Friedreich Ataxia / diagnosis*
  • Friedreich Ataxia / epidemiology
  • Friedreich Ataxia / genetics
  • Friedreich Ataxia / therapy*
  • Humans
  • Muscle, Skeletal / physiopathology
  • Neurophysiology / methods

Substances

  • Antioxidants