Abstract
We report a case of sudden unexplained death in a young asymptomatic woman in whom
postmortem genetic testing after a negative autopsy identified a homozygous pathogenic
mutation in SLC22A5 which leads clinically to primary carnitine deficiency (PCD). Her brother was subsequently
diagnosed clinically with short QT syndrome, received an implantable defibrillator,
and was then found to carry the same pathogenic homozygous mutation and critically
low levels of carnitine. His QT interval improved with the use of carnitine supplementation,
highlighting the close relationship between electrophysiology and biochemistry, and
the importance of postmortem genetic testing in the clinical management of surviving
relatives.
Résumé
Nous décrivons le cas de mort subite inexpliquée d’une jeune femme asymptomatique
chez qui les analyses génétiques post-mortem effectuées après une autopsie négative ont révélé une mutation homozygote pathogène
du gène SLC22A5 entraînant sur le plan clinique un déficit primaire en carnitine (DPC). Son frère,
chez qui un diagnostic clinique de syndrome du QT court a été posé ultérieurement,
a reçu un défibrillateur implantable. On a alors constaté qu’il était porteur de la
même mutation homozygote pathogène et qu’il présentait des concentrations de carnitine
dangereusement faibles. La prise de supplément de carnitine a donné lieu à une amélioration
de l’intervalle QT chez le patient, ce qui met en lumière la relation étroite qui
existe entre l’électrophysiologie et la biochimie, de même que l’importance des analyses
génétiques post-mortem dans la prise en charge clinique des proches survivants.
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References
- Carnitine transport and fatty acid oxidation.Biochim Biophys Acta. 2016; 1863: 2422-2435
- Diagnoses of newborns and mothers with carnitine uptake defects through newborn screening.Mol Genet Metab. 2010; 100: 46-50
- Functional genetic diversity in the high-affinity carnitine transporter OCTN2 (SLC22A5).Mol Pharmacol. 2006; 70: 1602-1611
- Carnitine deficiency induces a short QT syndrome.Heart Rhythm. 2016; 13: 165-174
Article info
Publication history
Published online: May 15, 2019
Accepted:
May 9,
2019
Received:
March 26,
2019
Footnotes
See page 1256.e2 for disclosure information.
Identification
Copyright
© 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
