title: Carnitine deficiency induces a short QT syndrome.
abstract: BACKGROUND
  Short QT syndrome is associated with an increased risk of cardiac arrhythmias and unexpected sudden death. Until now, only mutations in genes encoding the cardiac potassium and calcium channels have been implicated in early T-wave repolarization.
  
  
  OBJECTIVE
  The purpose of this study was to confirm a relationship between a short QT syndrome and carnitine deficiency.
  
  
  METHODS
  We report 3 patients affected by primary systemic carnitine deficiency and an associated short QT syndrome. Ventricular fibrillation during early adulthood was the initial symptom in 1 case. To confirm the relationship between carnitine, short QT syndrome, and arrhythmias, we used a mouse model of carnitine deficiency induced by long-term subcutaneous perfusion of MET88.
  
  
  RESULTS
  MET88-treated mice developed cardiac hypertrophy associated with a remodeling of the mitochondrial network. The continuous monitoring of electrocardiograms confirmed a shortening of the QT interval, which was negatively correlated with the plasma carnitine concentration. As in humans, such alterations coincided with the genesis of ventricular premature beats and ventricular tachycardia and fibrillation.
  
  
  CONCLUSIONS
  Altogether, these results suggest that long-chain fatty acid metabolism influence the morphology and the electrical function of the heart.
authors.affiliation: INSERM U1046, CNRS UMR 9214, Université de Montpellier, Montpellier, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Roussel
authors.affiliation: Médecine Pédiatrique, INSERM U1069, CHRU de Tours, Université François Rabelais, Tours, France.
authors.forename: François
authors.initials: F
authors.lastname: Labarthe
authors.affiliation: INSERM U1046, CNRS UMR 9214, Université de Montpellier, Montpellier, France.
authors.forename: Jerome
authors.initials: J
authors.lastname: Thireau
authors.affiliation: INSERM U1046, CNRS UMR 9214, Université de Montpellier, Montpellier, France; Médecine Pédiatrique, INSERM U1069, CHRU de Tours, Université François Rabelais, Tours, France.
authors.forename: Fabio
authors.initials: F
authors.lastname: Ferro
authors.affiliation: INSERM U1046, CNRS UMR 9214, Université de Montpellier, Montpellier, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Farah
authors.affiliation: INSERM U1046, CNRS UMR 9214, Université de Montpellier, Montpellier, France.
authors.forename: Jerome
authors.initials: J
authors.lastname: Roy
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Kagoshima University, Kagoshima, Japan.
authors.forename: Masahisa
authors.initials: M
authors.lastname: Horiuchi
authors.affiliation: Médecine Pédiatrique, INSERM U1069, CHRU de Tours, Université François Rabelais, Tours, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Tardieu
authors.affiliation: Médecine Pédiatrique, INSERM U1069, CHRU de Tours, Université François Rabelais, Tours, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Lefort
authors.affiliation: Laboratoire de Biochimie Hormonologie, Hôpital R Debré, AP-HP, Paris, France.
authors.forename: Jean
authors.initials: J
authors.lastname: François Benoist
authors.affiliation: INSERM U1046, CNRS UMR 9214, Université de Montpellier, Montpellier, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Lacampagne
authors.affiliation: INSERM U1046, CNRS UMR 9214, Université de Montpellier, Montpellier, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Richard
authors.affiliation: INSERM U1046, CNRS UMR 9214, Université de Montpellier, Montpellier, France.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Fauconnier
authors.affiliation: Service de Cardiologie, CHRU de Tours, Université François Rabelais, Tours, France. Electronic address: d.babuty@chu-tours.fr.
authors.forename: Dominique
authors.initials: D
authors.lastname: Babuty
authors.affiliation: INSERM U1046, CNRS UMR 9214, Université de Montpellier, Montpellier, France.
authors.forename: Jean Yves
authors.initials: JY
authors.lastname: Le Guennec
mesh_terms: D000328:Adult; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D009202:Cardiomyopathies / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D002331:Carnitine / Q000008:administration & dosage / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D002675:Child, Preschool; D015150:Echocardiography, Doppler / Q000379:methods; D004562:Electrocardiography / Q000379:methods; D022062:Electrophysiologic Techniques, Cardiac; D005260:Female; D006801:Humans; D022124:Hyperammonemia / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D007223:Infant; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008929:Mitochondria, Heart / Q000378:metabolism / Q000473:pathology; D009135:Muscular Diseases / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D016896:Treatment Outcome
chemical_list: D002331:Carnitine
keywords: Carnitine deficiency; Electrophysiological remodeling; Short QT syndrome; Sudden death; Ventricular arrhythmias