title: Arrhythmias and conduction defects as presenting symptoms of fatty acid oxidation disorders in children.
abstract: 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.
  
  
  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.
authors.affiliation: Service de Cardiologie Pédiatrique, Hôpital Necker-Enfants Malades, Paris, France. damien.bonnet@nck.ap-hop-paris.fr
authors.forename: D
authors.initials: D
authors.lastname: Bonnet
authors.forename: D
authors.initials: D
authors.lastname: Martin
authors.lastname: Pascale De Lonlay
authors.forename: E
authors.initials: E
authors.lastname: Villain
authors.forename: P
authors.initials: P
authors.lastname: Jouvet
authors.forename: D
authors.initials: D
authors.lastname: Rabier
authors.forename: M
authors.initials: M
authors.lastname: Brivet
authors.forename: J M
authors.initials: JM
authors.lastname: Saudubray
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000172:deficiency / Q000235:genetics; D042964:Acyl-CoA Dehydrogenase; D044942:Acyl-CoA Dehydrogenase, Long-Chain; D001145:Arrhythmias, Cardiac / Q000209:etiology*; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D002333:Carnitine Acyltransferases / Q000172:deficiency / Q000235:genetics; D002334:Carnitine O-Palmitoyltransferase / Q000172:deficiency / Q000235:genetics; D044943:Fatty Acid Desaturases / Q000172:deficiency / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006329:Heart Conduction System / Q000503:physiopathology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D063989:Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism*; D017240:Mitochondrial Myopathies / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D008954:Models, Biological; D010084:Oxidation-Reduction; D013398:Sudden Infant Death / Q000209:etiology; D017180:Tachycardia, Ventricular / Q000209:etiology
chemical_list: D005227:Fatty Acids; C116917:acylcarnitine; D015094:3-Hydroxyacyl CoA Dehydrogenases; D063989:Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase; D044943:Fatty Acid Desaturases; D042964:Acyl-CoA Dehydrogenase; D044942:Acyl-CoA Dehydrogenase, Long-Chain; D002333:Carnitine Acyltransferases; D002334:Carnitine O-Palmitoyltransferase; D002331:Carnitine