Friedreich’s ataxia

Friedreich’s ataxia (FRDA) is the most common autosomal recessive ataxia. This neurodegenerative disease is caused by expansion of a GAA triplet repeat located within the first intron of the frataxin gene on chormosome 9q13. There is clear correlation between the size of expanded repeat and severity of the phenotype. Clinically, FRDA is characterized by early-onset progressive gait and limb ataxia, dysarthria, loss of vibration and proprioceptive sense, areflexia, abnormal eye movements and extensor plantar response. Cardiomyopathy, diabetes, scoliosis and pes cavus are other common systemic complications. Frataxin is a mitochondrial protein that plays a role in iron homeostasis and deficiency of frataxin results in mitochondrial iron accumulation, defects in specific mitochondrial enzymes and oxidative damage. Therefore, FRDA treatment options have been mostly directed at antioxidant protection against mitochondrial damage. Available evidence seem to suggest that patients with FRDA should be treated with idebenone because it may reduce cardiac hypertrophy and at higher doses also improves neurologic function, although large controlled clinical trials are still needed. Alternatively, gene-based strategies for the treatment of FRDA may involve development of small molecules increasing frataxin gene transcription.

Category: Review
Volume: Vol. 55, No 2, april - june 2011
Authors: M. Čačić Hribljan, M. Jurin
Reference work:

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