This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bonnet, D. Articles by Saudubray, J.-M. Search for Related Content PubMed PubMed Citation Articles by Bonnet, D. Articles by Saudubray, J.-M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Arrhythmia Genetics Home Reference Related Collections Pediatric and congenital heart disease, including cardiovascular surgery Arrhythmias, clinical electrophysiology, drugs Oxidant stress

(Circulation. 1999;100:2248.)
© 1999 American Heart Association, Inc.

Clinical Investigation and Reports

Arrhythmias and Conduction Defects as Presenting Symptoms of Fatty Acid Oxidation Disorders in Children

Damien Bonnet, MD; Delphine Martin, MD; Pascale de Lonlay, MD; Elizabeth Villain, MD; Philippe Jouvet, MD; Daniel Rabier, MD; Michèle Brivet, MD; Jean-Marie Saudubray, MD

From the Service de Cardiologie Pédiatrique (D.B., E.V.), Service de Génétique et Maladies Métaboliques de l’Enfant (D.M., P.d.L., J.-M.S.), and Réanimation Pédiatrique (P.J.), Fédération de Pédiatrie, and the Département de Biochimie (D.R.), Hôpital Necker-Enfants Malades, Paris; and the Département de Biochimie (M.B.), Hôpital du Kremlin-Bicêtre, Kremlin-Bicêtre, France

Correspondence to Dr Damien Bonnet, Service de Cardiologie Pédiatrique, 149 Rue de Sèvres, 75015 Paris, France. E-mail damien.bonnet{at}nck.ap-hop-paris.fr

Background—The clinical manifestations of inherited disorders of fatty acid oxidation vary according to the enzymatic defect. They may present as isolated cardiomyopathy, sudden death, progressive skeletal myopathy, or hepatic failure. Arrhythmia is an unusual presenting symptom of fatty acid oxidation deficiencies.

Methods and Results—Over a period of 25 years, 107 patients were diagnosed with an inherited fatty acid oxidation disorder. Arrhythmia was the predominant presenting symptom in 24 cases. These 24 cases included 15 ventricular tachycardias, 4 atrial tachycardias, 4 sinus node dysfunctions with episodes of atrial tachycardia, 6 atrioventricular blocks, and 4 left bundle-branch blocks in newborn infants. Conduction disorders and atrial tachycardias were observed in patients with defects of long-chain fatty acid transport across the inner mitochondrial membrane (carnitine palmitoyl transferase type II deficiency and carnitine acylcarnitine translocase deficiency) and in patients with trifunctional protein deficiency. Ventricular tachycardias were observed in patients with any type of fatty acid oxidation deficiency. Arrhythmias were absent in patients with primary carnitine carrier, carnitine palmitoyl transferase I, and medium chain acyl coenzyme A dehydrogenase deficiencies.

Conclusions—The accumulation of arrhythmogenic intermediary metabolites of fatty acids, such as long-chain acylcarnitines, may be responsible for arrhythmias. Inborn errors of fatty acid oxidation should be considered in unexplained sudden death or near-miss in infants and in infants with conduction defects or ventricular tachycardia. Diagnosis can be easily ascertained by an acylcarnitine profile from blood spots on filter paper.

Key Words: metabolism • arrhythmia • fatty acids

This article has been cited by other articles:

				R. Gelinas, F. Labarthe, B. Bouchard, J. Mc Duff, G. Charron, M. E. Young, and C. Des Rosiers Alterations in carbohydrate metabolism and its regulation in PPAR{alpha} null mouse hearts Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1571 - H1580. [Abstract] [Full Text] [PDF]

				M. Liebig, I. Schymik, M. Mueller, U. Wendel, E. Mayatepek, J. Ruiter, A. W. Strauss, R. J.A. Wanders, and U. Spiekerkoetter Neonatal Screening for Very Long-Chain Acyl-CoA Dehydrogenase Deficiency: Enzymatic and Molecular Evaluation of Neonates With Elevated C14:1-Carnitine Levels Pediatrics, September 1, 2006; 118(3): 1065 - 1069. [Abstract] [Full Text] [PDF]

				V. J. Exil, C. D. Gardner, J. N. Rottman, H. Sims, B. Bartelds, Z. Khuchua, R. Sindhal, G. Ni, and A. W. Strauss Abnormal mitochondrial bioenergetics and heart rate dysfunction in mice lacking very-long-chain acyl-CoA dehydrogenase Am J Physiol Heart Circ Physiol, March 1, 2006; 290(3): H1289 - H1297. [Abstract] [Full Text] [PDF]

				P. Tavi, A. Hansson, S.-J. Zhang, N.-G. Larsson, and H. Westerblad Abnormal Ca2+ release and catecholamine-induced arrhythmias in mitochondrial cardiomyopathy Hum. Mol. Genet., April 15, 2005; 14(8): 1069 - 1076. [Abstract] [Full Text] [PDF]

				J. P.P. Smits, M. W. Veldkamp, and A. A.M. Wilde Mechanisms of inherited cardiac conduction disease Europace, January 1, 2005; 7(2): 122 - 137. [Abstract] [Full Text] [PDF]

				L. Lee, J. Horowitz, and M. Frenneaux Metabolic manipulation in ischaemic heart disease, a novel approach to treatment Eur. Heart J., April 2, 2004; 25(8): 634 - 641. [Abstract] [Full Text] [PDF]

				V.i. G. Davila-Roman, G. Vedala, P. Herrero, L. de las Fuentes, J. G. Rogers, D. P. Kelly, and R. J. Gropler Altered myocardial fatty acid and glucose metabolism in idiopathic dilated cardiomyopathy J. Am. Coll. Cardiol., July 17, 2002; 40(2): 271 - 277. [Abstract] [Full Text] [PDF]

				J. Marin-Garcia and M. J. Goldenthal Fatty acid metabolism in cardiac failure: biochemical, genetic and cellular analysis Cardiovasc Res, June 1, 2002; 54(3): 516 - 527. [Full Text] [PDF]

				H. Watkins Hypertrophic cardiomyopathy: from molecular and genetic mechanisms to clinical management Eur. Heart J. Suppl., October 1, 2001; 3(suppl_L): L43 - L50. [Abstract] [PDF]

				M. F. Oliver Prevention of Ventricular Fibrillation During Acute Myocardial Ischemia: Control of Free Fatty Acids Journal of Cardiovascular Pharmacology and Therapeutics, September 1, 2001; 6(3): 213 - 217. [Abstract] [PDF]

				J. C. Wood, M. J. Magera, P. Rinaldo, M. R. Seashore, A. W. Strauss, and A. Friedman Diagnosis of Very Long Chain Acyl-Dehydrogenase Deficiency From an Infant's Newborn Screening Card Pediatrics, July 1, 2001; 108(1): e19 - 19. [Abstract] [Full Text] [PDF]

				E. Blair, C. Redwood, H. Ashrafian, M. Oliveira, J. Broxholme, B. Kerr, A. Salmon, I. Ostman-Smith, and H. Watkins 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 Hum. Mol. Genet., May 1, 2001; 10(11): 1215 - 1220. [Abstract] [Full Text] [PDF]

				K. Kataoka, R. Nohara, R. Hosokawa, T. Hirai, K. Okuda, C. Li-Guang, Y. Fujibayashi, M. Fujita, J. Konishi, and S. Sasayama Myocardial Lipid Metabolism in Compensated and Advanced Stages of Heart Failure: Evaluation by Canine Pacing Model with BMIPP J. Nucl. Med., January 1, 2001; 42(1): 124 - 129. [Abstract] [Full Text] [PDF]

				E. Arbustini, P. Morbini, A. Pilotto, A. Gavazzi, and L. Tavazzi Familial dilated cardiomyopathy: from clinical presentation to molecular genetics Eur. Heart J., November 2, 2000; 21(22): 1825 - 1832. [PDF]