Diagnosis and treatment of Friedreich ataxia: a European perspective.

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.

• Authors: Jörg B Schulz, Sylvia Boesch, Katrin Bürk, Alexandra Dürr, Paola Giunti, Caterina Mariotti, Francoise Pousset, Ludger Schöls, Pierre Vankan, Massimo Pandolfo
• Journal: Nature reviews. Neurology (Nat Rev Neurol) Vol. 5 Issue 4 Pg. 222-34 (Apr 2009) ISSN: 1759-4766 [Electronic] England
• PMID: 19347027 (Publication Type: Journal Article, Review)

Chemical References

• Antioxidants

Topics

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