Cornea verticillata and acroparesthesia efficiently discriminate clusters of severity in Fabry disease.
BACKGROUD:Fabry disease (OMIM #301 500), the most prevalent lysosomal storage disease, is caused by enzymatic defects in alpha-galactosidase A (GLA gene; Xq22.1). Fabry disease has historically been characterized by progressive renal failure, early stroke and hypertrophic cardiomyopathy, with a dimi...
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doaj-689a2edfa43d4ed89aefddaf3cda906d2021-03-03T21:51:19ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01155e023346010.1371/journal.pone.0233460Cornea verticillata and acroparesthesia efficiently discriminate clusters of severity in Fabry disease.Wladimir MauhinOlivier BenvenisteDamien AmelinClémence MontagnerFoudil LamariCatherine CaillaudClaire DouillardBertrand DussolVanessa Leguy-SeguinPauline D'HalluinEsther NoelThierry ZenoneMarie MatignonFrançois MaillotKim-Heang LyGérard BessonMarjolaine WillemsFabien LabombardaAgathe MasseauChristian LavigneDidier LacombeHélène MaillardOlivier LidoveBACKGROUD:Fabry disease (OMIM #301 500), the most prevalent lysosomal storage disease, is caused by enzymatic defects in alpha-galactosidase A (GLA gene; Xq22.1). Fabry disease has historically been characterized by progressive renal failure, early stroke and hypertrophic cardiomyopathy, with a diminished life expectancy. A nonclassical phenotype has been described with an almost exclusive cardiac involvement. Specific therapies with enzyme substitution or chaperone molecules are now available depending on the mutation carried. Numerous clinical and fundamental studies have been conducted without stratifying patients by phenotype or severity, despite different prognoses and possible different pathophysiologies. We aimed to identify a simple and clinically relevant way to classify and stratify patients according to their disease severity. METHODS:Based on data from the French Fabry Biobank and Registry (FFABRY; n = 104; 54 males), we applied unsupervised multivariate statistics to determine clusters of patients and identify clinical criteria that would allow an effective classification of adult patients. Thanks to these criteria and empirical clinical considerations we secondly elaborate a new score that allow the severity stratification of patients. RESULTS:We observed that the absence of acroparesthesia or cornea verticillata is sufficient to classify males as having the nonclassical phenotype. We did not identify criteria that significantly cluster female patients. The classical phenotype was associated with a higher risk of severe renal (HR = 35.1; p <10-3) and cardiac events (HR = 4.8; p = 0.008) and a trend toward a higher risk of severe neurological events (HR = 7.7; p = 0.08) compared to nonclassical males. Our simple, rapid and clinically-relevant FFABRY score gave concordant results with the validated MSSI. CONCLUSION:Acroparesthesia and cornea verticillata are simple clinical criteria that efficiently stratify Fabry patients, defining 3 different groups: females and males with nonclassical and classical phenotypes of significantly different severity. The FFABRY score allows severity stratification of Fabry patients.https://doi.org/10.1371/journal.pone.0233460 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Wladimir Mauhin Olivier Benveniste Damien Amelin Clémence Montagner Foudil Lamari Catherine Caillaud Claire Douillard Bertrand Dussol Vanessa Leguy-Seguin Pauline D'Halluin Esther Noel Thierry Zenone Marie Matignon François Maillot Kim-Heang Ly Gérard Besson Marjolaine Willems Fabien Labombarda Agathe Masseau Christian Lavigne Didier Lacombe Hélène Maillard Olivier Lidove |
spellingShingle |
Wladimir Mauhin Olivier Benveniste Damien Amelin Clémence Montagner Foudil Lamari Catherine Caillaud Claire Douillard Bertrand Dussol Vanessa Leguy-Seguin Pauline D'Halluin Esther Noel Thierry Zenone Marie Matignon François Maillot Kim-Heang Ly Gérard Besson Marjolaine Willems Fabien Labombarda Agathe Masseau Christian Lavigne Didier Lacombe Hélène Maillard Olivier Lidove Cornea verticillata and acroparesthesia efficiently discriminate clusters of severity in Fabry disease. PLoS ONE |
author_facet |
Wladimir Mauhin Olivier Benveniste Damien Amelin Clémence Montagner Foudil Lamari Catherine Caillaud Claire Douillard Bertrand Dussol Vanessa Leguy-Seguin Pauline D'Halluin Esther Noel Thierry Zenone Marie Matignon François Maillot Kim-Heang Ly Gérard Besson Marjolaine Willems Fabien Labombarda Agathe Masseau Christian Lavigne Didier Lacombe Hélène Maillard Olivier Lidove |
author_sort |
Wladimir Mauhin |
title |
Cornea verticillata and acroparesthesia efficiently discriminate clusters of severity in Fabry disease. |
title_short |
Cornea verticillata and acroparesthesia efficiently discriminate clusters of severity in Fabry disease. |
title_full |
Cornea verticillata and acroparesthesia efficiently discriminate clusters of severity in Fabry disease. |
title_fullStr |
Cornea verticillata and acroparesthesia efficiently discriminate clusters of severity in Fabry disease. |
title_full_unstemmed |
Cornea verticillata and acroparesthesia efficiently discriminate clusters of severity in Fabry disease. |
title_sort |
cornea verticillata and acroparesthesia efficiently discriminate clusters of severity in fabry disease. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2020-01-01 |
description |
BACKGROUD:Fabry disease (OMIM #301 500), the most prevalent lysosomal storage disease, is caused by enzymatic defects in alpha-galactosidase A (GLA gene; Xq22.1). Fabry disease has historically been characterized by progressive renal failure, early stroke and hypertrophic cardiomyopathy, with a diminished life expectancy. A nonclassical phenotype has been described with an almost exclusive cardiac involvement. Specific therapies with enzyme substitution or chaperone molecules are now available depending on the mutation carried. Numerous clinical and fundamental studies have been conducted without stratifying patients by phenotype or severity, despite different prognoses and possible different pathophysiologies. We aimed to identify a simple and clinically relevant way to classify and stratify patients according to their disease severity. METHODS:Based on data from the French Fabry Biobank and Registry (FFABRY; n = 104; 54 males), we applied unsupervised multivariate statistics to determine clusters of patients and identify clinical criteria that would allow an effective classification of adult patients. Thanks to these criteria and empirical clinical considerations we secondly elaborate a new score that allow the severity stratification of patients. RESULTS:We observed that the absence of acroparesthesia or cornea verticillata is sufficient to classify males as having the nonclassical phenotype. We did not identify criteria that significantly cluster female patients. The classical phenotype was associated with a higher risk of severe renal (HR = 35.1; p <10-3) and cardiac events (HR = 4.8; p = 0.008) and a trend toward a higher risk of severe neurological events (HR = 7.7; p = 0.08) compared to nonclassical males. Our simple, rapid and clinically-relevant FFABRY score gave concordant results with the validated MSSI. CONCLUSION:Acroparesthesia and cornea verticillata are simple clinical criteria that efficiently stratify Fabry patients, defining 3 different groups: females and males with nonclassical and classical phenotypes of significantly different severity. The FFABRY score allows severity stratification of Fabry patients. |
url |
https://doi.org/10.1371/journal.pone.0233460 |
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