par Pandolfo, Massimo 
Editeur scientifique Rosenberg, R.;Pascual, Juan M.
Référence Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease, Academic Press, London, Ed. 5, page (833-843)
Publication Publié, 2015
Editeur scientifique Rosenberg, R.;Pascual, Juan M.
Référence Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease, Academic Press, London, Ed. 5, page (833-843)
Publication Publié, 2015
Partie d'ouvrage collectif
| Résumé : | Friedreich ataxia (FRDA) is an autosomal recessive disease characterized by progressive neurological and cardiac abnormalities. It has a prevalence of around 2×105 in whites, accounting for more than one-third of the cases of recessively inherited ataxia in this ethnic group. FRDA may not exist in nonwhite populations.The first symptoms usually appear in childhood, but age of onset may vary from infancy to adulthood. Atrophy of sensory and cerebellar pathways causes ataxia, dysarthria, fixation instability, deep sensory loss, and loss of tendon reflexes. Corticospinal degeneration leads to muscular weakness and extensor plantar responses. A hypertrophic cardiomyopathy may contribute to disability and cause premature death. Other common problems include kyphoscoliosis, pes cavus, and, in 10% of patients, diabetes mellitus.The FRDA gene (FXN) encodes a small mitochondrial protein, frataxin, which is produced in insufficient amounts in the disease, as a consequence of the epigenetic silencing of the gene triggered by a GAA triplet repeat expansion in the first intron of the gene. Frataxin deficiency results in impaired iron-sulfur cluster biogenesis in mitochondria, in turn leading to widespread dysfunction of iron-sulfur center containing enzymes (in particular respiratory complexes I, II and III, and aconitase), impaired iron metabolism, oxidative stress, and mitochondrial dysfunction. Therapy aims to restore frataxin levels or to correct the consequences of its deficiency. |
