Screening of Fabry disease in patients with an implanted permanent pacemaker.


Journal

International journal of cardiology
ISSN: 1874-1754
Titre abrégé: Int J Cardiol
Pays: Netherlands
ID NLM: 8200291

Informations de publication

Date de publication:
01 02 2023
Historique:
received: 12 09 2022
revised: 14 11 2022
accepted: 29 11 2022
pubmed: 7 12 2022
medline: 4 1 2023
entrez: 6 12 2022
Statut: ppublish

Résumé

Anderson-Fabry disease (AFD) is an X-linked inherited lysosomal disease caused by a defect in the gene encoding lysosomal enzyme α-galactosidase A (GLA). Atrio-ventricular (AV) nodal conduction defects and sinus node dysfunction are common complications of the disease. It is not fully elucidated how frequently AFD is responsible for acquired AV block or sinus node dysfunction and if some AFD patients could manifest primarily with spontaneous bradycardia in general population. The purpose of study was to evaluate the prevalence of AFD in male patients with implanted permanent pacemaker (PM). The prospective multicentric screening in consecutive male patients between 35 and 65 years with implanted PM for acquired third- or second- degree type 2 AV block or symptomatic second- degree type 1 AV block or sinus node dysfunction was performed. A total of 484 patients (mean age 54 ± 12 years at time of PM implantation) were enrolled to the screening in 12 local sites in Czech Republic. Out of all patients, negative result was found in 481 (99%) subjects. In 3 cases, a GLA variant was found, classified as benign: p.Asp313Tyr, p.D313Y). Pathogenic GLA variants (classical or non-classical form) or variants of unclear significance were not detected. The prevalence of pathogenic variants causing AFD in a general population sample with implanted permanent PM for AV conduction defects or sinus node dysfunction seems to be low. Our findings do not advocate a routine screening for AFD in all adult males with clinically significant bradycardia.

Sections du résumé

BACKGROUND
Anderson-Fabry disease (AFD) is an X-linked inherited lysosomal disease caused by a defect in the gene encoding lysosomal enzyme α-galactosidase A (GLA). Atrio-ventricular (AV) nodal conduction defects and sinus node dysfunction are common complications of the disease. It is not fully elucidated how frequently AFD is responsible for acquired AV block or sinus node dysfunction and if some AFD patients could manifest primarily with spontaneous bradycardia in general population. The purpose of study was to evaluate the prevalence of AFD in male patients with implanted permanent pacemaker (PM).
METHODS
The prospective multicentric screening in consecutive male patients between 35 and 65 years with implanted PM for acquired third- or second- degree type 2 AV block or symptomatic second- degree type 1 AV block or sinus node dysfunction was performed.
RESULTS
A total of 484 patients (mean age 54 ± 12 years at time of PM implantation) were enrolled to the screening in 12 local sites in Czech Republic. Out of all patients, negative result was found in 481 (99%) subjects. In 3 cases, a GLA variant was found, classified as benign: p.Asp313Tyr, p.D313Y). Pathogenic GLA variants (classical or non-classical form) or variants of unclear significance were not detected.
CONCLUSION
The prevalence of pathogenic variants causing AFD in a general population sample with implanted permanent PM for AV conduction defects or sinus node dysfunction seems to be low. Our findings do not advocate a routine screening for AFD in all adult males with clinically significant bradycardia.

Identifiants

pubmed: 36473604
pii: S0167-5273(22)01812-5
doi: 10.1016/j.ijcard.2022.11.062
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

71-75

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2022 Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest ZF and SH received the travel grants and speaker's honoraria from Takeda. GD received honoraria and travel funding from Sanofi Genzyme, Takeda, Protalix, and Greenovation Biotech GmbH. DG is a consultant for Amicus Therapeutics, Sanofi Genzyme, and Shire; has received research support from Sanofi Genzyme and Shire; and has received speaker honoraria and travel support from Amicus Therapeutics, Sanofi Genzyme, and Shire. AL received consultancy honoraria from Amicus Therapeutics, Sanofi Genzyme, Takeda, and speaker's honoraria from Sanofi Genzyme and Takeda.

Auteurs

Zdenka Fingrova (Z)

2(nd) Department of Medicine - Department of Cardiovascular Medicine of the 1(st) Faculty of Medicine, Charles Univesity, and General University Hospital in Prague, Prague, Czech Republic.

Stepan Havranek (S)

2(nd) Department of Medicine - Department of Cardiovascular Medicine of the 1(st) Faculty of Medicine, Charles Univesity, and General University Hospital in Prague, Prague, Czech Republic. Electronic address: stepan.havranek@lf1.cuni.cz.

Libor Sknouril (L)

Department of Cardiology, Cardiocenter, Hospital Podlesi, Trinec, Czech Republic.

Alan Bulava (A)

Department of Cardiology, Ceske Budejovice Hospital and Faculty of Health and Social Sciences, University of South Bohemia, Ceske Budejovice, Czech Republic.

Vlastimil Vancura (V)

Department of Cardiology, University Hospital and Faculty of Medicine Pilsen, Charles Univesity, Plzen, Czech Republic.

Milan Chovanec (M)

Cardiocenter, Department of Cardiology, Na Homolce Hospital, Prague, Czech Republic.

Vratislav Dedek (V)

Hospital Usti nad Orlici, Usti nad Orlici, Czech Republic.

Karol Curila (K)

Cardiocenter, 3(rd) Faculty of Medicine, Charles University and University Hospital Kralovske Vinohrady, Prague, Czech Republic.

Tomas Skala (T)

Cardiocenter, Department of Cardiology, University Hospital Olomouc, Olomouc, Czech Republic.

Jiri Jäger (J)

1(st) Department of Internal Medicine, University Hospital Hradec Kralove, Faculty of Medicine Hradec Kralove, Charles University, Hradec Kralove, Czech Republic.

Tomas Kluh (T)

Department of Cardiology, Regional Hospital Kladno, Kladno, Czech Republic.

Gabriela Dostalova (G)

2(nd) Department of Medicine - Department of Cardiovascular Medicine of the 1(st) Faculty of Medicine, Charles Univesity, and General University Hospital in Prague, Prague, Czech Republic.

Dominique P Germain (DP)

2(nd) Department of Medicine - Department of Cardiovascular Medicine of the 1(st) Faculty of Medicine, Charles Univesity, and General University Hospital in Prague, Prague, Czech Republic; Division of Medical Genetics, University of Versailles, Montigny, France.

Ales Linhart (A)

2(nd) Department of Medicine - Department of Cardiovascular Medicine of the 1(st) Faculty of Medicine, Charles Univesity, and General University Hospital in Prague, Prague, Czech Republic.

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Classifications MeSH