title: Cardiac energetics are abnormal in Friedreich ataxia patients in the absence of cardiac dysfunction and hypertrophy: an in vivo 31P magnetic resonance spectroscopy study.
abstract: OBJECTIVE
  Friedreich ataxia (FRDA), the commonest form of inherited ataxia, is often associated with cardiac hypertrophy and cardiac dysfunction is the most frequent cause of death. In 97%, FRDA is caused by a homoplasmic GAA triplet expansion in the FRDA gene on chromosome 9q13 that results in deficiency 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 determine whether bioenergetics deficit underlies the cardiac involvement in Friedreich ataxia (FRDA) we measured cardiac phosphocreatine to ATP ratio non-invasively in FRDA patients.
  
  
  RESULTS
  Eighteen FRDA patients and 18 sex- and age-matched controls were studied using phosphorus MR spectroscopy 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/ATP was also significantly reduced (P<0.0001).
  
  
  CONCLUSIONS
  Cardiac bioenergetics, 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 implies that cardiac metabolic dysfunction in FRDA precedes hypertrophy and is likely to play a role in its development.
authors.affiliation: MRC Biochemical and Clinical Magnetic Resonance Unit, Department of Biochemistry, University of Oxford and Oxford Radcliffe Hospital, Oxford, UK. lodi@med.unibo.it
authors.forename: R
authors.initials: R
authors.lastname: Lodi
authors.forename: B
authors.initials: B
authors.lastname: Rajagopalan
authors.forename: A M
authors.initials: AM
authors.lastname: Blamire
authors.forename: J M
authors.initials: JM
authors.lastname: Cooper
authors.forename: C H
authors.initials: CH
authors.lastname: Davies
authors.forename: J L
authors.initials: JL
authors.lastname: Bradley
authors.forename: P
authors.initials: P
authors.lastname: Styles
authors.forename: A H
authors.initials: AH
authors.lastname: Schapira
mesh_terms: D000255:Adenosine Triphosphate / Q000032:analysis*; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D016022:Case-Control Studies; D004452:Echocardiography; D005260:Female; D005621:Friedreich Ataxia / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D007501:Iron / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010725:Phosphocreatine / Q000032:analysis*
chemical_list: D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D007501:Iron