SLC22A5 – Short QT Syndrome

Autosomal recessive biallelic pathogenic variants in SLC22A5 have been reported to cause reversible short QT syndrome (Short QT syndrome). Two probands from separate case reports presented with homozygous c.67_69del (p.Phe23del) variants leading to systemic primary carnitine deficiency and marked QT‐interval abbreviation, which normalized upon L‐carnitine supplementation ([PMID:31472821]; [PMID:37658577]). In one family, a young woman died suddenly and her brother, who carried the same homozygous variant, demonstrated short QT and palpitations before receiving an implantable defibrillator and carnitine replacement, confirming segregation in one additional affected relative ([PMID:31472821]). A 13-year-old female with presyncope and palpitations exhibited left ventricular dysfunction and short QT due to the same in-frame deletion, with complete reversal of both electrical and mechanical abnormalities on carnitine therapy ([PMID:37658577]). These observations establish a causal link between OCTN2 deficiency and cardiac electrophysiology, with biochemical rescue supporting a pathogenic mechanism. Key Take-home: Screening for SLC22A5 variants in unexplained short QT syndrome enables targeted carnitine supplementation and prevention of arrhythmic death.

References

• The Canadian journal of cardiology • 2019 • Molecular Autopsy Implicates Primary Carnitine Deficiency in Sudden Unexplained Death and Reversible Short QT Syndrome PMID:31472821
• Annals of noninvasive electrocardiology • 2023 • Left ventricular noncompaction cardiomyopathy and short QT syndrome due to primary carnitine deficiency PMID:37658577

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