Iron Overload Leading to Torsades de Pointes in β-Thalassemia and Long QT Syndrome

Marwan M Refaat; Lea El Hage; Annette Buur Steffensen; Mostafa Hotait; Nicole Schmitt; Melvin Scheinman; Nitish Badhwar

doi:10.1016/j.ccep.2015.10.037

Iron Overload Leading to Torsades de Pointes in β-Thalassemia and Long QT Syndrome

Card Electrophysiol Clin. 2016 Mar;8(1):247-56. doi: 10.1016/j.ccep.2015.10.037.

Authors

Marwan M Refaat¹, Lea El Hage², Annette Buur Steffensen³, Mostafa Hotait⁴, Nicole Schmitt³, Melvin Scheinman², Nitish Badhwar⁵

Affiliations

¹ Cardiology Division, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon; Department of Biochemistry and Molecular Genetics, American University of Beirut Medical Center, Beirut, Lebanon; Cardiac Electrophysiology, Cardiology, Department of Internal Medicine, American University of Beirut Faculty of Medicine and Medical Center, 3 Dag Hammarskjold Plaza, 8th Floor, New York, NY 10017, USA; Department of Biochemistry and Molecular Genetics, American University of Beirut Faculty of Medicine and Medical Center, 3 Dag Hammarskjold Plaza, 8th Floor, New York, NY 10017, USA.
² Division of Cardiology, Department of Medicine, University of California San Francisco Medical Center, 500 Parnassus Avenue, MUE-431, San Francisco, CA 94143-1354, USA.
³ Department of Biomedical Sciences, Faculty of Health and Medical Sciences, Danish National Research Foundation Centre for Cardiac Arrhythmia, University of Copenhagen, Copenhagen, Denmark.
⁴ Cardiology Division, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
⁵ Division of Cardiology, Department of Medicine, University of California San Francisco Medical Center, 500 Parnassus Avenue, MUE-431, San Francisco, CA 94143-1354, USA. Electronic address: badhwar@medicine.ucsf.edu.

PMID: 26920202
DOI: 10.1016/j.ccep.2015.10.037

Abstract

The authors present a unique case of torsades de pointes in a β-thalassemia patient with early iron overload in the absence of any structural abnormalities as seen in hemochromatosis. Genetic testing showed a novel KCNQ1 gene mutation 1591C>T [Gln531Ter(X)]. Testing of the gene mutation in Xenopus laevis oocytes showed loss of function of the IKs current. The authors hypothesize that iron overload combined with the KCNQ1 gene mutation leads to prolongation of QTc and torsades de pointes.

Keywords: Iron overload; Long QT; β-thalassemia.

Publication types

Case Reports
Review

MeSH terms

Adult
Female
Humans
Iron Overload*
KCNQ1 Potassium Channel / genetics
Long QT Syndrome / complications*
Mutation / genetics
Torsades de Pointes*
Young Adult
beta-Thalassemia / complications*

Substances

KCNQ1 Potassium Channel
KCNQ1 protein, human