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

Abstract

Systemic primary carnitine deficiency is a rare genetic disease characterized by severe hypokinetic dilated cardiomyopathy and/or severe rhythm disorders. Without carnitine supplementation, evolution is usually towards a fatal cardiac decompensation. While the cardiomyopathy is most likely secondary to the energy deficiency, the mechanism of the rhythm disturbance is unclear, and may be related to a significant shortening of the QT interval. The aim of this work was to describe rhythmic manifestations at the diagnosis of primary carnitine deficiency and their evolution with carnitine supplementation. We conducted a retrospective multicenter study, including all French patients with a confirmed diagnosis of primary carnitine deficiency. Clinical and paraclinical data at diagnosis and during follow-up were collected. QT interval were measured by two pediatric cardiologists according to international recommendations and corrected with the Bazett formula (QTc). Nineteen patients (median age at diagnosis 2.3 years) followed in 8 French centers were included. At diagnosis, 22% of the patients (4/18) had arrhythmia (1 sudden death, 1 ventricular tachycardia and 2 ventricular fibrillations), and 78% (14/18) had a cardiomyopathy. Seven electrocardiograms before initiation of treatment out of the 9 available displayed a QTc < 340 ms indicating the diagnosis of short QT. The mean QTc after carnitine supplementation was 385 ± 24 ms versus 334 ± 21 ms before treatment ( P < 0.01). No patient reached the criteria of short QT syndrome with carnitine supplementation. Three patients died during the survey, which included one sudden death before carnitine supplementation, one non-recoverable rhythmic storm also before initiation of supplementation, and one sudden death in a patient who stopped carnitine supplementation 16 years after diagnosis. Primary carnitine deficiency is associated with a short QT interval that induces severe arrhythmias and sudden death. Carnitine supplementation normalizes the QTc and avoids arrhythmias. The screening of primary carnitine deficiency in neonates would prevent neonatal death.