Cardiac energetics are abnormal in Friedreich ataxia patients in the absence of cardiac dysfunction and hypertrophy: An in vivo P-31 magnetic resonance spectroscopy study

Objective: Friedreich ataxia (FRDA), the commonest form of inherited ataxia , is often associated with cardiac hypertrophy and cardiac dysfunction is t he most frequent cause of death. In 97%, FRDA is caused by a homoplasmic GA A triplet expansion in the FRDA gene on chromosome 9q13 that results in def iciency of frataxin, a mitochondrial protein of unknown function. There is evidence that frataxin deficiency leads to a severe defect of mitochondrial respiration associated with abnormal mitochondrial iron accumulation. To d etermine whether bioenergetics deficit underlies the cardiac involvement in Friedreich ataxia (FRDA) we measured cardiac phosphocreatine to ATP ratio non-invasively in FRDA patients. Methods and results: Eighteen FRDA patient s and 18 sex- and age-matched controls were studied using phosphorus MR spe ctroscopy and echocardiography. Left ventricular hypertrophy was present in eight FRDA patients while fractional shortening was normal in all. Cardiac PCr/ATP in FRDA patients as a group was reduced to 60% of the normal mean (P <0.0001). In the sub-group of patients with no cardiac hypertrophy PCr/A TP was also significantly reduced (P <0.0001). Conclusion: Cardiac bioenerg etics, measured in vivo, is abnormal in FRDA patients in the absence of any discernible deterioration in cardiac contractile performance. The altered bioenergetics found in FRDA patients without left ventricle hypertrophy imp lies that cardiac metabolic dysfunction in FRDA precedes hypertrophy and is likely to play a role in its development. (C) 2001 Elsevier Science B.V. A ll rights reserved.