Cardiomyopathy in Friedreich ataxia: clinical findings and research

Friedreich ataxia is the most common human ataxia and results from inadequate production of the frataxin protein, most often the result of a triplet expansion in the nuclear FXN gene. The gene cannot be transcribed to generate the messenger ribonucleic acid for frataxin. Frataxin is an iron-binding protein targeted to the mitochondrial matrix. In its absence, multiple iron-sulfur-dependent proteins in mitochondria and the cytosol lack proper assembly, destroying mitochondrial and nuclear function. Mitochondrial oxidant stress may also participate in ongoing cellular injury. Although progressive and debilitative ataxia is the most prominent clinical finding, hypertrophic cardiomyopathy with heart failure is the most common cause of early death in this disease. There is no cure. In this review the authors cover recent basic and clinical findings regarding the heart in Friedreich ataxia, offer recommendations for clinical management of the cardiomyopathy in this disease, and point out new research directions to advance the field.