Clinical characteristics of female Fabry disease patients with hypertrophic cardiomyopathy with mid-ventricular obstruction
Fabry disease (FD) is an X-linked lysosomal storage disease caused by mutations in GLA, which encodes α-galactosidase A (GLA). The loss or reduced activity of GLA leads to damage to multiple organs, resulting in the intracellular accumulation of globotriaosylceramide in various organs, including the...
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Elsevier
2025-03-01
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| Series: | Molecular Genetics and Metabolism Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214426925000114 |
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| author | Natsuko Inagaki Yasuyoshi Takei Tsuguhisa Hatano Yasuyuki Takada Yoshinao Yazaki Hisanori Kosuge Masatake Kobayashi Shinji Suzuki Tomohiro Umezu Masahiko Kuroda Kazuhiro Satomi Takeharu Hayashi |
| author_facet | Natsuko Inagaki Yasuyoshi Takei Tsuguhisa Hatano Yasuyuki Takada Yoshinao Yazaki Hisanori Kosuge Masatake Kobayashi Shinji Suzuki Tomohiro Umezu Masahiko Kuroda Kazuhiro Satomi Takeharu Hayashi |
| author_sort | Natsuko Inagaki |
| collection | DOAJ |
| description | Fabry disease (FD) is an X-linked lysosomal storage disease caused by mutations in GLA, which encodes α-galactosidase A (GLA). The loss or reduced activity of GLA leads to damage to multiple organs, resulting in the intracellular accumulation of globotriaosylceramide in various organs, including the heart, kidneys, and nervous system. Pathological changes in the heart typically result in concentric left ventricular hypertrophy. Hypertrophic cardiomyopathy (HCM) is an intractable disease characterized by unexplained left ventricular hypertrophy and diastolic dysfunction and is typically characterized by asymmetric left ventricular hypertrophy. We performed a causative gene analysis in patients with a rare subtype of HCM, HCM with mid-ventricular obstruction (HCM-MVO), and identified four patients with different pathogenic variants of GLA, which were clinically confirmed as FD. All four patients with FD and rare HCM-MVO morphology were female, and all cases involved the classical form of the disease. Three cases in whom lymphocyte Lyso-Gb3 was measured showed a marked decrease in Lyso-Gb3 after initiating enzyme replacement therapy (ERT). However, even after ERT, myocardial involvement worsened in the long term, and two patients experienced fatal arrhythmias. Therefore, it is difficult to determine the efficacy of myocardial involvement in FD using a lymphocyte-based Lyso-Gb3 assay system. In addition, none of these female patients had renal dysfunction, indicating a different pattern of organ damage compared with that previously reported in male patients. |
| format | Article |
| id | doaj-art-a27ec23a7d3846e5a9a93df04c84d21e |
| institution | Kabale University |
| issn | 2214-4269 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Genetics and Metabolism Reports |
| spelling | doaj-art-a27ec23a7d3846e5a9a93df04c84d21e2025-02-10T04:34:23ZengElsevierMolecular Genetics and Metabolism Reports2214-42692025-03-0142101196Clinical characteristics of female Fabry disease patients with hypertrophic cardiomyopathy with mid-ventricular obstructionNatsuko Inagaki0Yasuyoshi Takei1Tsuguhisa Hatano2Yasuyuki Takada3Yoshinao Yazaki4Hisanori Kosuge5Masatake Kobayashi6Shinji Suzuki7Tomohiro Umezu8Masahiko Kuroda9Kazuhiro Satomi10Takeharu Hayashi11Department of Cardiology, Tokyo Medical University, Tokyo, Japan; Department of Clinical Genetics Center, Tokyo Medical University, Tokyo, Japan; Corresponding author at: Department of Cardiology and Clinical Genetics Center, Tokyo Medical University, 6-7-1 Nishishinjyuku, Shinjyuku-ku, Tokyo 160-0023, Japan.Department of Cardiology, Tokyo Medical University, Tokyo, JapanDepartment of Cardiology, Tokyo Medical University, Tokyo, JapanDepartment of Cardiology, Tokyo Medical University, Tokyo, JapanDepartment of Cardiology, Tokyo Medical University, Tokyo, JapanDepartment of Cardiology, Tokyo Medical University, Tokyo, JapanDepartment of Cardiology, Tokyo Medical University, Tokyo, JapanDepartment of Pediatrics and Adolescent Medicine, Tokyo Medical University, Tokyo, JapanDepartment of Molecular Pathology, Tokyo Medical University, Tokyo, JapanDepartment of Clinical Genetics Center, Tokyo Medical University, Tokyo, Japan; Department of Molecular Pathology, Tokyo Medical University, Tokyo, JapanDepartment of Cardiology, Tokyo Medical University, Tokyo, JapanDepartment of Physiology, Tokai University School of Medicine, Isehara, JapanFabry disease (FD) is an X-linked lysosomal storage disease caused by mutations in GLA, which encodes α-galactosidase A (GLA). The loss or reduced activity of GLA leads to damage to multiple organs, resulting in the intracellular accumulation of globotriaosylceramide in various organs, including the heart, kidneys, and nervous system. Pathological changes in the heart typically result in concentric left ventricular hypertrophy. Hypertrophic cardiomyopathy (HCM) is an intractable disease characterized by unexplained left ventricular hypertrophy and diastolic dysfunction and is typically characterized by asymmetric left ventricular hypertrophy. We performed a causative gene analysis in patients with a rare subtype of HCM, HCM with mid-ventricular obstruction (HCM-MVO), and identified four patients with different pathogenic variants of GLA, which were clinically confirmed as FD. All four patients with FD and rare HCM-MVO morphology were female, and all cases involved the classical form of the disease. Three cases in whom lymphocyte Lyso-Gb3 was measured showed a marked decrease in Lyso-Gb3 after initiating enzyme replacement therapy (ERT). However, even after ERT, myocardial involvement worsened in the long term, and two patients experienced fatal arrhythmias. Therefore, it is difficult to determine the efficacy of myocardial involvement in FD using a lymphocyte-based Lyso-Gb3 assay system. In addition, none of these female patients had renal dysfunction, indicating a different pattern of organ damage compared with that previously reported in male patients.http://www.sciencedirect.com/science/article/pii/S2214426925000114Fabry diseaseHypertrophic cardiomyopathyMid-ventricular obstructionFemalePrognosis |
| spellingShingle | Natsuko Inagaki Yasuyoshi Takei Tsuguhisa Hatano Yasuyuki Takada Yoshinao Yazaki Hisanori Kosuge Masatake Kobayashi Shinji Suzuki Tomohiro Umezu Masahiko Kuroda Kazuhiro Satomi Takeharu Hayashi Clinical characteristics of female Fabry disease patients with hypertrophic cardiomyopathy with mid-ventricular obstruction Molecular Genetics and Metabolism Reports Fabry disease Hypertrophic cardiomyopathy Mid-ventricular obstruction Female Prognosis |
| title | Clinical characteristics of female Fabry disease patients with hypertrophic cardiomyopathy with mid-ventricular obstruction |
| title_full | Clinical characteristics of female Fabry disease patients with hypertrophic cardiomyopathy with mid-ventricular obstruction |
| title_fullStr | Clinical characteristics of female Fabry disease patients with hypertrophic cardiomyopathy with mid-ventricular obstruction |
| title_full_unstemmed | Clinical characteristics of female Fabry disease patients with hypertrophic cardiomyopathy with mid-ventricular obstruction |
| title_short | Clinical characteristics of female Fabry disease patients with hypertrophic cardiomyopathy with mid-ventricular obstruction |
| title_sort | clinical characteristics of female fabry disease patients with hypertrophic cardiomyopathy with mid ventricular obstruction |
| topic | Fabry disease Hypertrophic cardiomyopathy Mid-ventricular obstruction Female Prognosis |
| url | http://www.sciencedirect.com/science/article/pii/S2214426925000114 |
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