Systemic primary carnitine deficiency induces severe arrhythmia due to shortening of QT interval

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. We aim to describe rhythmic manifestations at diagnosis and with carnitine supplementation. 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. 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. 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.