This autosomal recessive neurodegenerative disorder is the most common inherited ataxia in man, with a prevalence of one in 50 000 and a carrier frequency of one in 120 Caucasians (Cossee et al. 1997). The disease is rare in sub-Saharan Africa and not found in the Far East. Friedreich's ataxia is characterized by degenerative disease involving the central and peripheral nervous system, notably manifesting as incoordination and, in some cases, with heart involvement. Ataxia describes marked incoordination of muscle movements. In Friedreich's ataxia, symptoms are usually present before adolescence with a slowly progressive sensory ataxia affecting gait; loss of tendon reflexes, position, and vibration sense; and difficulty with articulating speech (dysarthria). Over time cardiac involvement is seen in most patients including car-diomyopathy and arrhythmias; diabetes mellitus develops in a minority of patients. The disorder is usually fatal by the age of 50 years. Degeneration is seen involving the dorsal root ganglia, together with axonal degeneration in specific sites - notably the posterior columns and spinocerebellar and cor-ticospinal tracts.
stable transcriptionally inactive conformation (Sakamoto et al. 1999; Wells 2008). Frataxin is implicated in mitochondrial iron-sulphur cluster biosynthesis with dorsal root ganglia particularly sensitive to frataxin deficiency (Simon et al. 2004). The pathophysiology remains unclear but relates to iron dysregulation and oxidative stress (Orr and Zoghbi 2007).
Was this article helpful?