Cardiac involvement in creatine deficiency syndrome

Abstract Background Previous reports have demonstrated electrocardiographic and echocardiographic abnormalities consistent with early-stage cardiomyopathy in patients creatine transporter (CrT) deficiency, but cardiac involvement has never been accurately characterized. Purpose To investigate the phenotype associated deficiency a murine transgenic model syndrome (CDS). Methods Wild type CrT−/y mice (n=20) were serially evaluated vivo by electrocardiogram (EKG) echocardiography for six months, ex histological biochemical analyses. Nine CDS (n=4 L-arginine:glycine amidinotransferase - AGAT- n=5 CrT deficiency) underwent blood samples, including biomarkers, EKG, Holter monitoring, magnetic resonance (CMR). Results Compared to wild type, CRT−/y showed prolongation of QT interval (p=0.008) (Fig. 1), as well significant reduction ATP production from mitochondria (p<0.001) 2). No differences detected left ventricular systolic function, terms ejection fraction global longitudinal strain, along whole follow-up. Similarly, 3 also prolonged QTc (median 515 ms), while other 2 had borderline at no tachyarrhythmias could be observed. subject abnormal diastolic function. At CMR, an increase native T1 value was reported 4 subjects 1076 ms) AGAT 1 extracellular volume matching detection late gadolinium enhancement. Finally, level plasma norepinephrine. Familiar carriers (3 CrT) notable functional alterations, except subjects. Conclusion Prolonged is observed deficiency. Biohumoral signs neurohormonal activation initial replacement fibrosis – latter suggested are identified their clinical significance remains determined. Funding Acknowledgement Type funding sources: None.