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Fabry Disease and the Heart: A Comprehensive Review

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations of the GLA gene that result in a deficiency of the enzymatic activity of α-galactosidase A and consequent accumulation of glycosphingolipids in body fluids and lysosomes of the cells throughout the body. GB3 accumulatio...

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Autores principales: Azevedo, Olga, Cordeiro, Filipa, Gago, Miguel Fernandes, Miltenberger-Miltenyi, Gabriel, Ferreira, Catarina, Sousa, Nuno, Cunha, Damião
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123068/
https://www.ncbi.nlm.nih.gov/pubmed/33922740
http://dx.doi.org/10.3390/ijms22094434
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author Azevedo, Olga
Cordeiro, Filipa
Gago, Miguel Fernandes
Miltenberger-Miltenyi, Gabriel
Ferreira, Catarina
Sousa, Nuno
Cunha, Damião
author_facet Azevedo, Olga
Cordeiro, Filipa
Gago, Miguel Fernandes
Miltenberger-Miltenyi, Gabriel
Ferreira, Catarina
Sousa, Nuno
Cunha, Damião
author_sort Azevedo, Olga
collection PubMed
description Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations of the GLA gene that result in a deficiency of the enzymatic activity of α-galactosidase A and consequent accumulation of glycosphingolipids in body fluids and lysosomes of the cells throughout the body. GB3 accumulation occurs in virtually all cardiac cells (cardiomyocytes, conduction system cells, fibroblasts, and endothelial and smooth muscle vascular cells), ultimately leading to ventricular hypertrophy and fibrosis, heart failure, valve disease, angina, dysrhythmias, cardiac conduction abnormalities, and sudden death. Despite available therapies and supportive treatment, cardiac involvement carries a major prognostic impact, representing the main cause of death in FD. In the last years, knowledge has substantially evolved on the pathophysiological mechanisms leading to cardiac damage, the natural history of cardiac manifestations, the late-onset phenotypes with predominant cardiac involvement, the early markers of cardiac damage, the role of multimodality cardiac imaging on the diagnosis, management and follow-up of Fabry patients, and the cardiac efficacy of available therapies. Herein, we provide a comprehensive and integrated review on the cardiac involvement of FD, at the pathophysiological, anatomopathological, laboratory, imaging, and clinical levels, as well as on the diagnosis and management of cardiac manifestations, their supportive treatment, and the cardiac efficacy of specific therapies, such as enzyme replacement therapy and migalastat.
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spelling pubmed-81230682021-05-16 Fabry Disease and the Heart: A Comprehensive Review Azevedo, Olga Cordeiro, Filipa Gago, Miguel Fernandes Miltenberger-Miltenyi, Gabriel Ferreira, Catarina Sousa, Nuno Cunha, Damião Int J Mol Sci Review Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations of the GLA gene that result in a deficiency of the enzymatic activity of α-galactosidase A and consequent accumulation of glycosphingolipids in body fluids and lysosomes of the cells throughout the body. GB3 accumulation occurs in virtually all cardiac cells (cardiomyocytes, conduction system cells, fibroblasts, and endothelial and smooth muscle vascular cells), ultimately leading to ventricular hypertrophy and fibrosis, heart failure, valve disease, angina, dysrhythmias, cardiac conduction abnormalities, and sudden death. Despite available therapies and supportive treatment, cardiac involvement carries a major prognostic impact, representing the main cause of death in FD. In the last years, knowledge has substantially evolved on the pathophysiological mechanisms leading to cardiac damage, the natural history of cardiac manifestations, the late-onset phenotypes with predominant cardiac involvement, the early markers of cardiac damage, the role of multimodality cardiac imaging on the diagnosis, management and follow-up of Fabry patients, and the cardiac efficacy of available therapies. Herein, we provide a comprehensive and integrated review on the cardiac involvement of FD, at the pathophysiological, anatomopathological, laboratory, imaging, and clinical levels, as well as on the diagnosis and management of cardiac manifestations, their supportive treatment, and the cardiac efficacy of specific therapies, such as enzyme replacement therapy and migalastat. MDPI 2021-04-23 /pmc/articles/PMC8123068/ /pubmed/33922740 http://dx.doi.org/10.3390/ijms22094434 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Azevedo, Olga
Cordeiro, Filipa
Gago, Miguel Fernandes
Miltenberger-Miltenyi, Gabriel
Ferreira, Catarina
Sousa, Nuno
Cunha, Damião
Fabry Disease and the Heart: A Comprehensive Review
title Fabry Disease and the Heart: A Comprehensive Review
title_full Fabry Disease and the Heart: A Comprehensive Review
title_fullStr Fabry Disease and the Heart: A Comprehensive Review
title_full_unstemmed Fabry Disease and the Heart: A Comprehensive Review
title_short Fabry Disease and the Heart: A Comprehensive Review
title_sort fabry disease and the heart: a comprehensive review
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123068/
https://www.ncbi.nlm.nih.gov/pubmed/33922740
http://dx.doi.org/10.3390/ijms22094434
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