Friedreich ataxia.
There has been rapid progress in the understanding of several aspects of Friedreich's ataxia (FA) since the gene mutation was identified in 1996. At the clinical level, now it is possible to confirm that the majority of patients fullfilling clinical criteria for classic FA have the FA gene mutation but some do not, indicating genetic heterogeneity. Also, the phenotype associated with the FA mutation is much wider than that defined by clinical criteria and includes ataxia with retained or brisk reflexes as well as late onset ataxia with or without retained reflexes. It is now clear that the unstable GAA expansion that underlies FA causes a deficiency of the mitochondrial protein frataxin, leading to potentially harmful oxidative injury associated with excessive iron deposits in mitochondria. In addition, pathogenesis may involve a primary defect in synthesis of iron-sulfur cluster containing enzymes. Therapeutic attempts are already using anti-oxidant strategies and such efforts are likely to be enhanced by the rapid availability of animal models of the disease.
Pandolfo
Massimo
M
Department of Neurology, Erasme Hospital, Brussels Free University, Brussels, Belgium.
D002648:Child; D005621:Friedreich Ataxia / Q000150:complications / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D006801:Humans