Aurore Curie, PhD, MD: “CREAT_criteria Study: What have we learned regarding the cardiac phenotype of patients with creatine transporter deficiency (SLC6A8)?”

ABSTRACT

Creatine Transporter Deficiency (CTD) is a rare genetic disorder related to SLC6A8 pathogenic variants, leading to moderate to severe intellectual disability. Little is known about the cardiac consequences of the disease. A model of CTD in mice suggested a risk of sudden cardiac death. Long QTc interval, frequent premature ventricular contractions (PVCs) and left ventricular dilatation (LVD) were reported in some CTD patients. In order to determine the cardiac CTD patient phenotype, we performed a prospective study on 24 French male CTD patient including resting 12-lead ECG, 24-hour ambulatory ECG and transthoracic echocardiography (TTE). We present here preliminary results on the first 17 CTD patients included (mean age 17.5 ± 4.2 years). 24-hour ambulatory ECG was impossible in 2 patients. No patient had syncope. No patient had LVD, or LV systolic dysfunction. LV posterior wall thinning was observed in only one patient. On resting 12-lead ECG, prominent U-waves were common (80%) and the QTc was of normal duration in all patients when U-waves were excluded (429.5 ± 21.5 ms). 24-hour ambulatory ECG revealed an abnormal intermittent ECG pattern, associating paroxysmal prominent U-waves (100%) and paroxysmal biphasic T-waves ( 93.3 %). PVCs were rare (30.1 ± 79.2 per 24h). Contrary to what was suggested in the literature, we did not find any long QTc interval (after exclusion of U-waves) or LVD. We documented abnormal ventricular repolarization pattern with prominent U-waves and biphasic T-waves. Cardiac follow-up is needed.