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The Heart in Friedreich's Ataxia: Basic Findings and Clinical Implications

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Date 2011 Jun 22
PMID 21691434
Citations 17
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Abstract

Friedreich's Ataxia is the most common inherited ataxia in man. It is a mitochondrial disease caused by severely reduced expression of the iron binding protein, frataxin. A large GAA triplet expansion in the human FRDA gene encoding this protein inhibits expression of this gene. It is inherited in an autosomal recessive pattern and typically diagnosed in childhood. The primary symptoms include severe and progressive neuropathy, and a hypertrophic cardiomyopathy that may cause death. The cardiomyopathy is difficult to treat and is frequently associated with arrhythmias, heart failure, and intolerance of cardiovascular stress, such as surgeries. Innovative approaches to therapy, such as histone deacetylase inhibitors, and enzyme replacement with cell penetrant peptide fusion proteins, hold promise for this and other similar mitochondrial disorders. This review will focus on the basic findings of this disease, and the cardiomyopathy associated with its diagnosis.

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References
1.
Filla A, De Michele G, Marconi R, Bucci L, Carillo C, Castellano A . Prevalence of hereditary ataxias and spastic paraplegias in Molise, a region of Italy. J Neurol. 1992; 239(6):351-3. DOI: 10.1007/BF00867594. View

2.
Nichol H, Gakh O, ONeill H, Pickering I, Isaya G, George G . Structure of frataxin iron cores: an X-ray absorption spectroscopic study. Biochemistry. 2003; 42(20):5971-6. DOI: 10.1021/bi027021l. View

3.
Al-Mahdawi S, Mouro Pinto R, Ismail O, Varshney D, Lymperi S, Sandi C . The Friedreich ataxia GAA repeat expansion mutation induces comparable epigenetic changes in human and transgenic mouse brain and heart tissues. Hum Mol Genet. 2007; 17(5):735-46. DOI: 10.1093/hmg/ddm346. View

4.
Gaizo Moore V, Payne R . Transactivator of transcription fusion protein transduction causes membrane inversion. J Biol Chem. 2004; 279(31):32541-4. DOI: 10.1074/jbc.M405930200. View

5.
Richardson D . Friedreich's ataxia: iron chelators that target the mitochondrion as a therapeutic strategy?. Expert Opin Investig Drugs. 2003; 12(2):235-45. DOI: 10.1517/13543784.12.2.235. View