Danon disease is an underdiagnosed cause of advanced heart
failure in young female patients: a LAMP2 flow cytometric study

J 2020

Danon disease is an underdiagnosed cause of advanced heart failure in young female patients: a LAMP2 flow cytometric study

GURKA, Jiri, Lenka PIHEROVA, Filip MAJER, Anna CHALOUPKA, Daniela ŽÁKOVÁ et. al.

Basic information

Original name

Danon disease is an underdiagnosed cause of advanced heart failure in young female patients: a LAMP2 flow cytometric study

Authors

GURKA, Jiri (203 Czech Republic), Lenka PIHEROVA (203 Czech Republic), Filip MAJER (203 Czech Republic), Anna CHALOUPKA (203 Czech Republic, belonging to the institution), Daniela ŽÁKOVÁ (203 Czech Republic), Ondrej PELAK (203 Czech Republic), Alice KREBSOVA (203 Czech Republic), Petr PEICHL (203 Czech Republic), Jan KREJČÍ (203 Czech Republic, belonging to the institution), Tomáš FREIBERGER (203 Czech Republic), Vojtech MELENOVSKY (203 Czech Republic), Josef KAUTZNER (203 Czech Republic), Tomas KALINA (203 Czech Republic), Jakub SIKORA (203 Czech Republic) and Milos KUBANEK (203 Czech Republic, guarantor)

Edition

ESC Heart Failure, San Francisco, Wiley Periodicals, 2020, 2055-5822

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30201 Cardiac and Cardiovascular systems

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.411

RIV identification code

RIV/00216224:14110/20:00116651

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1002/ehf2.12823

UT WoS

000573314800056

Keywords in English

Advanced heart failure; Danon disease; Lysosomal-associated membrane protein type 2; Screening; White blood cells

Abstract

V originále

Aims Danon disease (DD) is a rare X-linked disorder caused by mutations in the lysosomal-associated membrane protein type 2 gene (LAMP2). DD is difficult to distinguish from other causes of dilated or hypertrophic cardiomyopathy (HCM) in female patients. As DD female patients regularly progress into advanced heart failure (AHF) aged 20-40 years, their early identification is critical to improve patient survival and facilitate genetic counselling. In this study, we evaluated the prevalence of DD among female patients with non-ischemic cardiomyopathy, who reached AHF and were younger than 40 years. Methods and results The study cohort comprised 60 female patients: 47 (78%) heart transplant recipients, 2 (3%) patients treated with ventricular assist device, and 11 (18%) patients undergoing pre-transplant assessment. Aetiology of the cardiomyopathy was known in 15 patients (including two DD patients). LAMP2 expression in peripheral white blood cells (WBC) was tested by flow cytometry (FC) in the remaining 45 female patients. Whole exome sequencing was used as an alternative independent testing method to FC. Five additional female DD patients (two with different novelLAMP2mutations) were identified by FC. The total prevalence of DD in this cohort was 12%. HCM phenotype (57% vs. 9%,*P = 0.022) and delta waves identified by electrocardiography (43% vs. 0%,*P = 0.002) were significantly more frequent in DD female patients. Conclusions Danon disease is an underdiagnosed cause of AHF in young female patients. LAMP2 expression testing in peripheral WBCs by FC can be used as an effective screening/diagnostic tool to identify DD in this patient population.

Citovat

GURKA, Jiri, Lenka PIHEROVA, Filip MAJER, Anna CHALOUPKA, Daniela ŽÁKOVÁ, Ondrej PELAK, Alice KREBSOVA, Petr PEICHL, Jan KREJČÍ, Tomáš FREIBERGER, Vojtech MELENOVSKY, Josef KAUTZNER, Tomas KALINA, Jakub SIKORA and Milos KUBANEK. Danon disease is an underdiagnosed cause of advanced heart failure in young female patients: a LAMP2 flow cytometric study. ESC Heart Failure. San Francisco: Wiley Periodicals, 2020, vol. 7, No 5, p. 2534-2543. ISSN 2055-5822. Available from: https://dx.doi.org/10.1002/ehf2.12823.

@article{1685078,
   author = {Gurka, Jiri and Piherova, Lenka and Majer, Filip and Chaloupka, Anna and Žáková, Daniela and Pelak, Ondrej and Krebsova, Alice and Peichl, Petr and Krejčí, Jan and Freiberger, Tomáš and Melenovsky, Vojtech and Kautzner, Josef and Kalina, Tomas and Sikora, Jakub and Kubanek, Milos},
   article_location = {San Francisco},
   article_number = {5},
   doi = {http://dx.doi.org/10.1002/ehf2.12823},
   keywords = {Advanced heart failure; Danon disease; Lysosomal-associated membrane protein type 2; Screening; White blood cells},
   language = {eng},
   issn = {2055-5822},
   journal = {ESC Heart Failure},
   title = {Danon disease is an underdiagnosed cause of advanced heart failure in young female patients: a LAMP2 flow cytometric study},
   url = {https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.12823},
   volume = {7},
   year = {2020}
}

TY  - JOUR
ID  - 1685078
AU  - Gurka, Jiri - Piherova, Lenka - Majer, Filip - Chaloupka, Anna - Žáková, Daniela - Pelak, Ondrej - Krebsova, Alice - Peichl, Petr - Krejčí, Jan - Freiberger, Tomáš - Melenovsky, Vojtech - Kautzner, Josef - Kalina, Tomas - Sikora, Jakub - Kubanek, Milos
PY  - 2020
TI  - Danon disease is an underdiagnosed cause of advanced heart failure in young female patients: a LAMP2 flow cytometric study
JF  - ESC Heart Failure
VL  - 7
IS  - 5
SP  - 2534-2543
EP  - 2534-2543
PB  - Wiley Periodicals
SN  - 20555822
KW  - Advanced heart failure
KW  - Danon disease
KW  - Lysosomal-associated membrane protein type 2
KW  - Screening
KW  - White blood cells
UR  - https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.12823
L2  - https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.12823
N2  - Aims Danon disease (DD) is a rare X-linked disorder caused by mutations in the lysosomal-associated membrane protein type 2 gene (LAMP2). DD is difficult to distinguish from other causes of dilated or hypertrophic cardiomyopathy (HCM) in female patients. As DD female patients regularly progress into advanced heart failure (AHF) aged 20-40 years, their early identification is critical to improve patient survival and facilitate genetic counselling. In this study, we evaluated the prevalence of DD among female patients with non-ischemic cardiomyopathy, who reached AHF and were younger than 40 years. Methods and results The study cohort comprised 60 female patients: 47 (78%) heart transplant recipients, 2 (3%) patients treated with ventricular assist device, and 11 (18%) patients undergoing pre-transplant assessment. Aetiology of the cardiomyopathy was known in 15 patients (including two DD patients). LAMP2 expression in peripheral white blood cells (WBC) was tested by flow cytometry (FC) in the remaining 45 female patients. Whole exome sequencing was used as an alternative independent testing method to FC. Five additional female DD patients (two with different novelLAMP2mutations) were identified by FC. The total prevalence of DD in this cohort was 12%. HCM phenotype (57% vs. 9%,*P = 0.022) and delta waves identified by electrocardiography (43% vs. 0%,*P = 0.002) were significantly more frequent in DD female patients. Conclusions Danon disease is an underdiagnosed cause of AHF in young female patients. LAMP2 expression testing in peripheral WBCs by FC can be used as an effective screening/diagnostic tool to identify DD in this patient population.
ER  -

GURKA, Jiri, Lenka PIHEROVA, Filip MAJER, Anna CHALOUPKA, Daniela ŽÁKOVÁ, Ondrej PELAK, Alice KREBSOVA, Petr PEICHL, Jan KREJČÍ, Tomáš FREIBERGER, Vojtech MELENOVSKY, Josef KAUTZNER, Tomas KALINA, Jakub SIKORA and Milos KUBANEK. Danon disease is an underdiagnosed cause of advanced heart failure in young female patients: a LAMP2 flow cytometric study. \textit{ESC Heart Failure}. San Francisco: Wiley Periodicals, 2020, vol.~7, No~5, p.~2534-2543. ISSN~2055-5822. Available from: https://dx.doi.org/10.1002/ehf2.12823.

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