Fabry Disease in Women: Genetic Basis, Available Biomarkers, and Clinical Manifestations
Fabry Disease (FD) is a rare lysosomal storage disorder caused by mutations in the <i>GLA</i> gene on the X chromosome, leading to a deficiency in α-galactosidase A (AGAL) enzyme activity. This leads to the accumulation of glycosphingolipids, primarily globotriaosylceramide (Gb3), in vit...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/15/1/37 |
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| author | Raafiah Izhar Margherita Borriello Antonella La Russa Rossella Di Paola Ananya De Giovambattista Capasso Diego Ingrosso Alessandra F. Perna Mariadelina Simeoni |
| author_facet | Raafiah Izhar Margherita Borriello Antonella La Russa Rossella Di Paola Ananya De Giovambattista Capasso Diego Ingrosso Alessandra F. Perna Mariadelina Simeoni |
| author_sort | Raafiah Izhar |
| collection | DOAJ |
| description | Fabry Disease (FD) is a rare lysosomal storage disorder caused by mutations in the <i>GLA</i> gene on the X chromosome, leading to a deficiency in α-galactosidase A (AGAL) enzyme activity. This leads to the accumulation of glycosphingolipids, primarily globotriaosylceramide (Gb3), in vital organs such as the kidneys, heart, and nervous system. While FD was initially considered predominantly affecting males, recent studies have uncovered that heterozygous Fabry women, carrying a single mutated <i>GLA</i> gene, can manifest a wide array of clinical symptoms, challenging the notion of asymptomatic carriers. The mechanisms underlying the diverse clinical manifestations in females remain not fully understood due to X-chromosome inactivation (XCI). XCI also known as “lyonization”, involves the random inactivation of one of the two X chromosomes. This process is considered a potential factor influencing phenotypic variation. This review delves into the complex landscape of FD in women, discussing its genetic basis, the available biomarkers, clinical manifestations, and the potential impact of XCI on disease severity. Additionally, it highlights the challenges faced by heterozygous Fabry women, both in terms of their disease burden and interactions with healthcare professionals. Current treatment options, including enzyme replacement therapy, are discussed, along with the need for healthcare providers to be well-informed about FD in women, ultimately contributing to improved patient care and quality of life. |
| first_indexed | 2024-03-08T10:54:50Z |
| format | Article |
| id | doaj.art-f6bcd542bc544f9e954dcc394cd67571 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-08T10:54:50Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-f6bcd542bc544f9e954dcc394cd675712024-01-26T16:41:34ZengMDPI AGGenes2073-44252023-12-011513710.3390/genes15010037Fabry Disease in Women: Genetic Basis, Available Biomarkers, and Clinical ManifestationsRaafiah Izhar0Margherita Borriello1Antonella La Russa2Rossella Di Paola3Ananya De4Giovambattista Capasso5Diego Ingrosso6Alessandra F. Perna7Mariadelina Simeoni8Department of Mental and Physical Health and Preventive Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Sperimental Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, ItalyDepartment of Mental and Physical Health and Preventive Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Mental and Physical Health and Preventive Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyBiogem S.c.a.r.l. Research Institute, 83031 Ariano Irpino, ItalyDepartment of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyNephrology and Dialysis Unit, Department of Translation Medical Sciences, University of Campania “Luigi Vanvitelli”, 80131 Naples, ItalyNephrology and Dialysis Unit, Department of Translation Medical Sciences, University of Campania “Luigi Vanvitelli”, 80131 Naples, ItalyFabry Disease (FD) is a rare lysosomal storage disorder caused by mutations in the <i>GLA</i> gene on the X chromosome, leading to a deficiency in α-galactosidase A (AGAL) enzyme activity. This leads to the accumulation of glycosphingolipids, primarily globotriaosylceramide (Gb3), in vital organs such as the kidneys, heart, and nervous system. While FD was initially considered predominantly affecting males, recent studies have uncovered that heterozygous Fabry women, carrying a single mutated <i>GLA</i> gene, can manifest a wide array of clinical symptoms, challenging the notion of asymptomatic carriers. The mechanisms underlying the diverse clinical manifestations in females remain not fully understood due to X-chromosome inactivation (XCI). XCI also known as “lyonization”, involves the random inactivation of one of the two X chromosomes. This process is considered a potential factor influencing phenotypic variation. This review delves into the complex landscape of FD in women, discussing its genetic basis, the available biomarkers, clinical manifestations, and the potential impact of XCI on disease severity. Additionally, it highlights the challenges faced by heterozygous Fabry women, both in terms of their disease burden and interactions with healthcare professionals. Current treatment options, including enzyme replacement therapy, are discussed, along with the need for healthcare providers to be well-informed about FD in women, ultimately contributing to improved patient care and quality of life.https://www.mdpi.com/2073-4425/15/1/37Fabry disease<i>GLA</i> genegenetic basisX-chromosome inactivationclinical manifestationstherapies |
| spellingShingle | Raafiah Izhar Margherita Borriello Antonella La Russa Rossella Di Paola Ananya De Giovambattista Capasso Diego Ingrosso Alessandra F. Perna Mariadelina Simeoni Fabry Disease in Women: Genetic Basis, Available Biomarkers, and Clinical Manifestations Genes Fabry disease <i>GLA</i> gene genetic basis X-chromosome inactivation clinical manifestations therapies |
| title | Fabry Disease in Women: Genetic Basis, Available Biomarkers, and Clinical Manifestations |
| title_full | Fabry Disease in Women: Genetic Basis, Available Biomarkers, and Clinical Manifestations |
| title_fullStr | Fabry Disease in Women: Genetic Basis, Available Biomarkers, and Clinical Manifestations |
| title_full_unstemmed | Fabry Disease in Women: Genetic Basis, Available Biomarkers, and Clinical Manifestations |
| title_short | Fabry Disease in Women: Genetic Basis, Available Biomarkers, and Clinical Manifestations |
| title_sort | fabry disease in women genetic basis available biomarkers and clinical manifestations |
| topic | Fabry disease <i>GLA</i> gene genetic basis X-chromosome inactivation clinical manifestations therapies |
| url | https://www.mdpi.com/2073-4425/15/1/37 |
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