FRDA
MIM.606829 9q13
Frataxin deficiency is the main cause of Friedreich ataxia, an autosomal recessive neurodegenerative disorder. Frataxin function in mitochondria has not been fully explained yet bu frataxin interacts functionally with mitochondrial electron transport chain proteins and is involved in mitochondrial iron metabolism.
Pathology
mutations in FRDA gene encoding frataxin.
Pathogenesis
Mitochondria obtained from heart biopsies of Friedreich ataxia patients have disclosed specific defects in the citric-acid cycle enzyme aconitase, and complex I-III activities.
The causative Friedreich ataxia protein, dubbed frataxin, has an essential role in mitochondrial iron homeostasis, and Friedreich ataxia can therefore be considered as an OXPHOS homeostasis defect.
References
Shoubridge EA. Nuclear genetic defects of oxidative phosphorylation. Hum Mol Genet. 2001 Oct 1;10(20):2277-84. PMID: #11673411#
Smeitink J, van den Heuvel L, DiMauro S. The genetics and pathology of oxidative phosphorylation. Nat Rev Genet. 2001 May;2(5):342-52. PMID: #11331900#