Danon disease is an underdiagnosed cause of advanced heart failure in young female patients: a LAMP2 flow cytometric study
Abstract 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 prog...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-10-01
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| Series: | ESC Heart Failure |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/ehf2.12823 |
| _version_ | 1818906034597527552 |
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| author | Jiri Gurka Lenka Piherova Filip Majer Anna Chaloupka Daniela Zakova Ondrej Pelak Alice Krebsova Petr Peichl Jan Krejci Tomas Freiberger Vojtech Melenovsky Josef Kautzner Tomas Kalina Jakub Sikora Milos Kubanek |
| author_facet | Jiri Gurka Lenka Piherova Filip Majer Anna Chaloupka Daniela Zakova Ondrej Pelak Alice Krebsova Petr Peichl Jan Krejci Tomas Freiberger Vojtech Melenovsky Josef Kautzner Tomas Kalina Jakub Sikora Milos Kubanek |
| author_sort | Jiri Gurka |
| collection | DOAJ |
| description | Abstract 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 novel LAMP2 mutations) 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. |
| first_indexed | 2024-12-19T21:32:49Z |
| format | Article |
| id | doaj.art-f82c5a15de5141a49aaf81de1fa209bd |
| institution | Directory Open Access Journal |
| issn | 2055-5822 |
| language | English |
| last_indexed | 2024-12-19T21:32:49Z |
| publishDate | 2020-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | ESC Heart Failure |
| spelling | doaj.art-f82c5a15de5141a49aaf81de1fa209bd2022-12-21T20:04:53ZengWileyESC Heart Failure2055-58222020-10-01752534254310.1002/ehf2.12823Danon disease is an underdiagnosed cause of advanced heart failure in young female patients: a LAMP2 flow cytometric studyJiri Gurka0Lenka Piherova1Filip Majer2Anna Chaloupka3Daniela Zakova4Ondrej Pelak5Alice Krebsova6Petr Peichl7Jan Krejci8Tomas Freiberger9Vojtech Melenovsky10Josef Kautzner11Tomas Kalina12Jakub Sikora13Milos Kubanek14Department of Cardiology Institute for Clinical and Experimental Medicine Prague Czech RepublicResearch Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine Charles University and General University Hospital Prague Czech RepublicResearch Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine Charles University and General University Hospital Prague Czech Republic1st Internal Cardioangiologic Clinic, Faculty of Medicine Masaryk University and St. Anne's University Hospital Brno Czech RepublicCentre of Cardiovascular and Transplant Surgery St. Annes University Hospital Brno Czech RepublicDepartment of Paediatric Haematology and Oncology, Childhood Leukaemia Investigation Prague, Second Faculty of Medicine Charles University and University Hospital Motol Prague Czech RepublicDepartment of Cardiology Institute for Clinical and Experimental Medicine Prague Czech RepublicDepartment of Cardiology Institute for Clinical and Experimental Medicine Prague Czech Republic1st Internal Cardioangiologic Clinic, Faculty of Medicine Masaryk University and St. Anne's University Hospital Brno Czech RepublicCentre of Cardiovascular and Transplant Surgery St. Annes University Hospital Brno Czech RepublicDepartment of Cardiology Institute for Clinical and Experimental Medicine Prague Czech RepublicDepartment of Cardiology Institute for Clinical and Experimental Medicine Prague Czech RepublicDepartment of Paediatric Haematology and Oncology, Childhood Leukaemia Investigation Prague, Second Faculty of Medicine Charles University and University Hospital Motol Prague Czech RepublicResearch Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine Charles University and General University Hospital Prague Czech RepublicDepartment of Cardiology Institute for Clinical and Experimental Medicine Prague Czech RepublicAbstract 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 novel LAMP2 mutations) 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.https://doi.org/10.1002/ehf2.12823Advanced heart failureDanon diseaseLysosomal‐associated membrane protein type 2ScreeningWhite blood cells |
| spellingShingle | Jiri Gurka Lenka Piherova Filip Majer Anna Chaloupka Daniela Zakova Ondrej Pelak Alice Krebsova Petr Peichl Jan Krejci Tomas Freiberger Vojtech Melenovsky Josef Kautzner Tomas Kalina Jakub Sikora Milos Kubanek Danon disease is an underdiagnosed cause of advanced heart failure in young female patients: a LAMP2 flow cytometric study ESC Heart Failure Advanced heart failure Danon disease Lysosomal‐associated membrane protein type 2 Screening White blood cells |
| title | Danon disease is an underdiagnosed cause of advanced heart failure in young female patients: a LAMP2 flow cytometric study |
| title_full | Danon disease is an underdiagnosed cause of advanced heart failure in young female patients: a LAMP2 flow cytometric study |
| title_fullStr | Danon disease is an underdiagnosed cause of advanced heart failure in young female patients: a LAMP2 flow cytometric study |
| title_full_unstemmed | Danon disease is an underdiagnosed cause of advanced heart failure in young female patients: a LAMP2 flow cytometric study |
| title_short | Danon disease is an underdiagnosed cause of advanced heart failure in young female patients: a LAMP2 flow cytometric study |
| title_sort | danon disease is an underdiagnosed cause of advanced heart failure in young female patients a lamp2 flow cytometric study |
| topic | Advanced heart failure Danon disease Lysosomal‐associated membrane protein type 2 Screening White blood cells |
| url | https://doi.org/10.1002/ehf2.12823 |
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