Journal Article Ppublish 13 citations
PubMed: 37979236 DOI: 10.1016/j.ymgme.2023.107733
Systemic primary carnitine deficiency induces severe arrhythmia due to shortening of QT interval.
Mol Genet Metab 140(4):107733
Authors: Pierre Lodewyckx, Jean Issa, Margaux Gaschignard, Delphine Lamireau, Pascale De Lonlay, Aude Servais, Magalie Barth, Sandy Courapied, Gilles Morin, Nadir Benbrik, François Maillot, Dominique Babuty, François Labarthe, Bruno Lefort
Affiliations
- Institut des Cardiopathies Congénitales de Tours and FHU PRECICARE, CHU Tours, Tours, France.
- CCMR Maladies Métaboliques, CHU Bordeaux, Bordeaux, France.
- Maladie métabolique, Hôpital Necker Enfant Malade, APHP, Université Paris Cité, Filière G2M, MetabERN, Paris, France.
- Maladie métabolique, CHU Angers, Angers, France.
- Maladie métabolique, CHU Lille, Filière G2M, MetabERN, Lille, France.
- Maladie métabolique, CHU Amiens, Amiens, France.
- Fédération cardiologie pédiatrique, CHU Nantes, Nantes, France.
- CRMR Maladies Héréditaires du Métabolisme ToTeM, CHU Tours, Tours, France.
- Cardiologie, CHU Tours, Tours, France.
- CRMR Maladies Héréditaires du Métabolisme ToTeM, CHU Tours, Tours, France; INSERM UMR 1069, Université de Tours, Tours, France.
- Institut des Cardiopathies Congénitales de Tours and FHU PRECICARE, CHU Tours, Tours, France; INSERM UMR 1069, Université de Tours, Tours, France.
Abstract
BACKGROUND
Systemic primary carnitine deficiency (PCD) is characterized by cardiomyopathy and arrhythmia. Without carnitine supplementation, progression is usually towards fatal cardiac decompensation. While the cardiomyopathy is most likely secondary to energy deficiency, the mechanism of arrhythmia is unclear, and may be related to a short QT interval.
OBJECTIVE
We aim to describe rhythmic manifestations at diagnosis and with carnitine supplementation.
METHODS
French patients diagnosed for PCD were retrospectively included. Clinical and para clinical data at diagnosis and during follow-up were collected. Electrocardiograms with QT interval measurements were blinded reviewed by two paediatric cardiologists.
RESULTS
Nineteen patients (median age at diagnosis 2.3 years (extremes 0.3-28.9)) followed in 8 French centres were included. At diagnosis, 21% of patients (4/19) had arrhythmia (2 ventricular fibrillations, 1 ventricular tachycardia and 1 sudden death), and 84% (16/19) had cardiomyopathy. Six electrocardiograms before treatment out of 11 available displayed a short QT (QTc < 340 ms). Median corrected QTc after carnitine supplementation was 404 ms (extremes 341-447) versus 350 ms (extremes 282-421) before treatment (p < 0.001). The whole QTc was prolonged, and no patient reached the criterion of short QT syndrome with carnitine supplementation. Three patients died, probably from rhythmic cause without carnitine supplementation (two extra-hospital sudden deaths and one non-recoverable rhythmic storm before carnitine supplementation), whereas no rhythmic complication occurred in patients with carnitine supplementation.
CONCLUSION
PCD is associated with shortening of the QT interval inducing severe arrhythmia. A potential explanation would be a toxic effect of accumulated fatty acid and metabolites on ionic channels embedded in the cell membrane. Carnitine supplementation normalizes the QTc and prevents arrhythmia. Newborn screening of primary carnitine deficiency would prevent avoidable deaths.
MeSH
Carnitine, Death, Sudden, Metabolic Diseases, Molecular Biology, Arrhythmias, Cardiac, Diagnosis, Therapeutics, Cardiomyopathies