Cardiac energetics correlates to myocardial hypertrophy in Friedreich's ataxia

Friedreich's ataxia is a neurodegenerative disease frequently associated with hypertrophic cardiomyopathy. We have determined mitochondrial ATP, phosphocreatine, and intracellular inorganic phosphate levels by 31P nuclear magnetic resonance spectroscopy in the heart of 11 Friedreich's ataxia patients and 11 healthy controls. For the first time, to our knowledge, we showed a significant correlation between the extent of myocardial energy deficiency and the degree of myocardial hypertrophy. When combining our results with previous works on Friedreich's ataxia, these novel findings suggest that energy metabolism is most likely the cause and hypertrophy the effect in Friedreich's ataxia. Ann Neurol 2003;53:000–000

[1]  A. Blamire,et al.  Cardiac energetics are abnormal in Friedreich ataxia patients in the absence of cardiac dysfunction and hypertrophy: an in vivo 31P magnetic resonance spectroscopy study. , 2001, Cardiovascular research.

[2]  H. Watkins,et al.  Mutations in the gamma(2) subunit of AMP-activated protein kinase cause familial hypertrophic cardiomyopathy: evidence for the central role of energy compromise in disease pathogenesis. , 2001, Human molecular genetics.

[3]  J. Melki,et al.  Mouse models for Friedreich ataxia exhibit cardiomyopathy, sensory nerve defect and Fe-S enzyme deficiency followed by intramitochondrial iron deposits , 2001, Nature Genetics.

[4]  L. Schöls,et al.  The GAA repeat expansion in intron 1 of the frataxin gene is related to the severity of cardiac manifestation in patients with Friedreich's ataxia , 2001, Journal of Molecular Medicine.

[5]  C. Kahn,et al.  Frataxin activates mitochondrial energy conversion and oxidative phosphorylation. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[6]  A. Munnich,et al.  Effect of idebenone on cardiomyopathy in Friedreich's ataxia: a preliminary study , 1999, The Lancet.

[7]  O. Lutz,et al.  31P NMR spectroscopy detects metabolic abnormalities in asymptomatic patients with hypertrophic cardiomyopathy. , 1998, Circulation.

[8]  W. Mckenna,et al.  Experience from clinical genetics in hypertrophic cardiomyopathy: proposal for new diagnostic criteria in adult members of affected families. , 1997, Heart.