The Spanish Fabry women study: a retrospective observational study describing the phenotype of females with GLA variants
Background: Fabry disease (FD) is an X-linked condition caused by variants in the GLA gene. Since females have two X chromosomes, they were historically thought to be carriers. Although increased knowledge has shown that females often develop the disease, data from Spain and other countries reported...
| Autores: | , , , , , , , , , , , , |
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| Formato: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2023 |
| País: | España |
| Recursos: | Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
| Repositorio: | r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
| OAI Identifier: | oai:iibsantpau.fundanetsuite.com:p15923 |
| Acesso em linha: | https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=15923 https://www.scopus.com/inward/record.uri?eid=2-s2.0-85145955880&doi=10.1186%2fs13023-022-02599-w&partnerID=40&md5=47551e9518db32c27efdd55f42c5a575 |
| Access Level: | acceso abierto |
| Palavra-chave: | osteocalcin adult age aged Article brain blood vessel clinical feature cohort analysis comorbidity controlled study cornea verticillata disease management Europe Fabry disease family female follow up frameshift mutation gastrointestinal tract gene deletion gene identification genetic association genetic screening genetic variability GLA gene heat hemangiokeratoma heterozygote hospital human kidney major clinical study missense mutation nonsense mutation observational study peripheral nervous system phenotype protein blood level retrospective study Spaniard cognition genetics hereditary corneal dystrophy Cognition Corneal Dystrophies, Hereditary Fabry Disease Female Humans Phenotype Retrospective Studies |
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The Spanish Fabry women study: a retrospective observational study describing the phenotype of females with GLA variantsSánchez R.Ripoll-Vera T.López-Mendoza M.de Juan-Ribera J.Gimeno J.R.Hermida Á.Ruz-Zafra M.A.Torregrosa J.V.Mora A.García-Pinilla J.M.Fortuny E.Aguinaga-Barrilero A.Torra R.osteocalcinadultageagedArticlebrain blood vesselclinical featurecohort analysiscomorbiditycontrolled studycornea verticillatadisease managementEuropeFabry diseasefamilyfemalefollow upframeshift mutationgastrointestinal tractgene deletiongene identificationgenetic associationgenetic screeninggenetic variabilityGLA geneheathemangiokeratomaheterozygotehospitalhumankidneymajor clinical studymissense mutationnonsense mutationobservational studyperipheral nervous systemphenotypeprotein blood levelretrospective studySpaniardcognitionFabry diseasegeneticshereditary corneal dystrophyphenotypeCognitionCorneal Dystrophies, HereditaryFabry DiseaseFemaleHumansPhenotypeRetrospective StudiesBackground: Fabry disease (FD) is an X-linked condition caused by variants in the GLA gene. Since females have two X chromosomes, they were historically thought to be carriers. Although increased knowledge has shown that females often develop the disease, data from Spain and other countries reported that females were undertreated. The aim of this study was to provide a wider and more recent description of the disease characteristics and associated management of females with a GLA variant in a Spanish cohort. Results: Ninety-seven females from 12 hospitals were included in this retrospective study. Mean age was 50.1 ± 17.2 years. Median follow-up time from GLA variant identification was 36.1 months, and most (70.1%) were identified through family screening. Variants associated with classic/non-classic phenotypes were similarly distributed (40.2%/53.6%). Missense variants were the most prevalent (n = 84, 86.6%). In the overall group, 70.4% had major organ involvement (i.e., cardiac, renal, cerebrovascular, peripheral nervous system or gastrointestinal), and 47.3% also had typical Fabry signs (angiokeratoma, cornea verticillata or increased plasma lyso-Gb3). Cardiac involvement was the most prevalent (49.5%) and the main reason for treatment initiation. A total of 33 (34%) patients received disease-specific therapy, 55% of whom were diagnosed by family screening. Females carrying variants associated with a classic phenotype had higher frequencies of clinical manifestations (92.3%) and were predominant in the treated subgroup (69.7%). Despite this, there were 34 untreated females (56.7% of total untreated), with both phenotypes represented, who had major organ involvement, with 27 of cardiac, renal or cerebrovascular nature. Age or comorbidities in this subgroup were comparable to the treated subgroup (P = 0.8 and P = 0.8, respectively). Conclusions: Efforts have been made in recent years to diagnose and treat timely Fabry females in Spain. A high percentage of females with pathogenic variants, regardless of their associated phenotype, will likely develop disease. A proportion of females with severe disease in this cohort received specific treatment. Still a significant number of females, even with same profile as the treated ones, who may be eligible for treatment according to European recommendations, remained untreated. Reasons for this merit further investigation. © 2023, The Author(s).BMC2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=15923https://www.scopus.com/inward/record.uri?eid=2-s2.0-85145955880&doi=10.1186%2fs13023-022-02599-w&partnerID=40&md5=47551e9518db32c27efdd55f42c5a575Orphanet Journal of Rare DiseasesISSN: 17501172reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p159232026-06-14T12:41:47Z |
| dc.title.none.fl_str_mv |
The Spanish Fabry women study: a retrospective observational study describing the phenotype of females with GLA variants |
| title |
The Spanish Fabry women study: a retrospective observational study describing the phenotype of females with GLA variants |
| spellingShingle |
The Spanish Fabry women study: a retrospective observational study describing the phenotype of females with GLA variants Sánchez R. osteocalcin adult age aged Article brain blood vessel clinical feature cohort analysis comorbidity controlled study cornea verticillata disease management Europe Fabry disease family female follow up frameshift mutation gastrointestinal tract gene deletion gene identification genetic association genetic screening genetic variability GLA gene heat hemangiokeratoma heterozygote hospital human kidney major clinical study missense mutation nonsense mutation observational study peripheral nervous system phenotype protein blood level retrospective study Spaniard cognition Fabry disease genetics hereditary corneal dystrophy phenotype Cognition Corneal Dystrophies, Hereditary Fabry Disease Female Humans Phenotype Retrospective Studies |
| title_short |
The Spanish Fabry women study: a retrospective observational study describing the phenotype of females with GLA variants |
| title_full |
The Spanish Fabry women study: a retrospective observational study describing the phenotype of females with GLA variants |
| title_fullStr |
The Spanish Fabry women study: a retrospective observational study describing the phenotype of females with GLA variants |
| title_full_unstemmed |
The Spanish Fabry women study: a retrospective observational study describing the phenotype of females with GLA variants |
| title_sort |
The Spanish Fabry women study: a retrospective observational study describing the phenotype of females with GLA variants |
| dc.creator.none.fl_str_mv |
Sánchez R. Ripoll-Vera T. López-Mendoza M. de Juan-Ribera J. Gimeno J.R. Hermida Á. Ruz-Zafra M.A. Torregrosa J.V. Mora A. García-Pinilla J.M. Fortuny E. Aguinaga-Barrilero A. Torra R. |
| author |
Sánchez R. |
| author_facet |
Sánchez R. Ripoll-Vera T. López-Mendoza M. de Juan-Ribera J. Gimeno J.R. Hermida Á. Ruz-Zafra M.A. Torregrosa J.V. Mora A. García-Pinilla J.M. Fortuny E. Aguinaga-Barrilero A. Torra R. |
| author_role |
author |
| author2 |
Ripoll-Vera T. López-Mendoza M. de Juan-Ribera J. Gimeno J.R. Hermida Á. Ruz-Zafra M.A. Torregrosa J.V. Mora A. García-Pinilla J.M. Fortuny E. Aguinaga-Barrilero A. Torra R. |
| author2_role |
author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
osteocalcin adult age aged Article brain blood vessel clinical feature cohort analysis comorbidity controlled study cornea verticillata disease management Europe Fabry disease family female follow up frameshift mutation gastrointestinal tract gene deletion gene identification genetic association genetic screening genetic variability GLA gene heat hemangiokeratoma heterozygote hospital human kidney major clinical study missense mutation nonsense mutation observational study peripheral nervous system phenotype protein blood level retrospective study Spaniard cognition Fabry disease genetics hereditary corneal dystrophy phenotype Cognition Corneal Dystrophies, Hereditary Fabry Disease Female Humans Phenotype Retrospective Studies |
| topic |
osteocalcin adult age aged Article brain blood vessel clinical feature cohort analysis comorbidity controlled study cornea verticillata disease management Europe Fabry disease family female follow up frameshift mutation gastrointestinal tract gene deletion gene identification genetic association genetic screening genetic variability GLA gene heat hemangiokeratoma heterozygote hospital human kidney major clinical study missense mutation nonsense mutation observational study peripheral nervous system phenotype protein blood level retrospective study Spaniard cognition Fabry disease genetics hereditary corneal dystrophy phenotype Cognition Corneal Dystrophies, Hereditary Fabry Disease Female Humans Phenotype Retrospective Studies |
| description |
Background: Fabry disease (FD) is an X-linked condition caused by variants in the GLA gene. Since females have two X chromosomes, they were historically thought to be carriers. Although increased knowledge has shown that females often develop the disease, data from Spain and other countries reported that females were undertreated. The aim of this study was to provide a wider and more recent description of the disease characteristics and associated management of females with a GLA variant in a Spanish cohort. Results: Ninety-seven females from 12 hospitals were included in this retrospective study. Mean age was 50.1 ± 17.2 years. Median follow-up time from GLA variant identification was 36.1 months, and most (70.1%) were identified through family screening. Variants associated with classic/non-classic phenotypes were similarly distributed (40.2%/53.6%). Missense variants were the most prevalent (n = 84, 86.6%). In the overall group, 70.4% had major organ involvement (i.e., cardiac, renal, cerebrovascular, peripheral nervous system or gastrointestinal), and 47.3% also had typical Fabry signs (angiokeratoma, cornea verticillata or increased plasma lyso-Gb3). Cardiac involvement was the most prevalent (49.5%) and the main reason for treatment initiation. A total of 33 (34%) patients received disease-specific therapy, 55% of whom were diagnosed by family screening. Females carrying variants associated with a classic phenotype had higher frequencies of clinical manifestations (92.3%) and were predominant in the treated subgroup (69.7%). Despite this, there were 34 untreated females (56.7% of total untreated), with both phenotypes represented, who had major organ involvement, with 27 of cardiac, renal or cerebrovascular nature. Age or comorbidities in this subgroup were comparable to the treated subgroup (P = 0.8 and P = 0.8, respectively). Conclusions: Efforts have been made in recent years to diagnose and treat timely Fabry females in Spain. A high percentage of females with pathogenic variants, regardless of their associated phenotype, will likely develop disease. A proportion of females with severe disease in this cohort received specific treatment. Still a significant number of females, even with same profile as the treated ones, who may be eligible for treatment according to European recommendations, remained untreated. Reasons for this merit further investigation. © 2023, The Author(s). |
| publishDate |
2023 |
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2023 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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Inglés |
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Orphanet Journal of Rare Diseases ISSN: 17501172 reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
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