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A classical phenotype of Anderson-Fabry disease in a female patient with intronic mutations of the GLA gene: a case report

BACKGROUND: Fabry disease (FD) is a hereditary metabolic disorder caused by the partial or total inactivation of a lysosomal hydrolase, the enzyme α-galactosidase A (GLA). This inactivation is responsible for the storage of undegraded glycosphingolipids in the lysosomes with subsequent cellular and...

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Autores principales: Pisani, Antonio, Imbriaco, Massimo, Zizzo, Carmela, Albeggiani, Giuseppe, Colomba, Paolo, Alessandro, Riccardo, Iemolo, Francesco, Duro, Giovanni
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3425126/
https://www.ncbi.nlm.nih.gov/pubmed/22682330
http://dx.doi.org/10.1186/1471-2261-12-39
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author Pisani, Antonio
Imbriaco, Massimo
Zizzo, Carmela
Albeggiani, Giuseppe
Colomba, Paolo
Alessandro, Riccardo
Iemolo, Francesco
Duro, Giovanni
author_facet Pisani, Antonio
Imbriaco, Massimo
Zizzo, Carmela
Albeggiani, Giuseppe
Colomba, Paolo
Alessandro, Riccardo
Iemolo, Francesco
Duro, Giovanni
author_sort Pisani, Antonio
collection PubMed
description BACKGROUND: Fabry disease (FD) is a hereditary metabolic disorder caused by the partial or total inactivation of a lysosomal hydrolase, the enzyme α-galactosidase A (GLA). This inactivation is responsible for the storage of undegraded glycosphingolipids in the lysosomes with subsequent cellular and microvascular dysfunction. The incidence of disease is estimated at 1:40,000 in the general population, although neonatal screening initiatives have found an unexpectedly high prevalence of genetic alterations, up to 1:3,100, in newborns in Italy, and have identified a surprisingly high frequency of newborn males with genetic alterations (about 1:1,500) in Taiwan. CASE PRESENTATION: We describe the case of a 40-year-old female patient who presented with transient ischemic attack (TIA), discomfort in her hands, intolerance to cold and heat, severe angina and palpitations, chronic kidney disease. Clinical, biochemical and molecular studies were performed. CONCLUSIONS: Reported symptoms, peculiar findings in a renal biopsy – the evidence of occasional lamellar inclusions in podocytes and mesangial cells – and left ventricular (LV) hypertrophy, which are considered to be specific features of FD, as well as molecular evaluations, suggested the diagnosis of a classical form of FD. We detected four mutations in the GLA gene of the patient: -10C>T (g.1170C>T), c.370-77_-81del (g.7188-7192del5), c.640-16A>G (g.10115A>G), c.1000-22C>T (g.10956C>T). These mutations, located in promoter and intronic regulatory regions, have been observed in several patients with manifestations of FD. In our patient clinical picture showed a multisystemic involvement with early onset of symptoms, thus suggesting that these intronic mutations can be found even in patients with classical form of FD.
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spelling pubmed-34251262012-08-23 A classical phenotype of Anderson-Fabry disease in a female patient with intronic mutations of the GLA gene: a case report Pisani, Antonio Imbriaco, Massimo Zizzo, Carmela Albeggiani, Giuseppe Colomba, Paolo Alessandro, Riccardo Iemolo, Francesco Duro, Giovanni BMC Cardiovasc Disord Case Report BACKGROUND: Fabry disease (FD) is a hereditary metabolic disorder caused by the partial or total inactivation of a lysosomal hydrolase, the enzyme α-galactosidase A (GLA). This inactivation is responsible for the storage of undegraded glycosphingolipids in the lysosomes with subsequent cellular and microvascular dysfunction. The incidence of disease is estimated at 1:40,000 in the general population, although neonatal screening initiatives have found an unexpectedly high prevalence of genetic alterations, up to 1:3,100, in newborns in Italy, and have identified a surprisingly high frequency of newborn males with genetic alterations (about 1:1,500) in Taiwan. CASE PRESENTATION: We describe the case of a 40-year-old female patient who presented with transient ischemic attack (TIA), discomfort in her hands, intolerance to cold and heat, severe angina and palpitations, chronic kidney disease. Clinical, biochemical and molecular studies were performed. CONCLUSIONS: Reported symptoms, peculiar findings in a renal biopsy – the evidence of occasional lamellar inclusions in podocytes and mesangial cells – and left ventricular (LV) hypertrophy, which are considered to be specific features of FD, as well as molecular evaluations, suggested the diagnosis of a classical form of FD. We detected four mutations in the GLA gene of the patient: -10C>T (g.1170C>T), c.370-77_-81del (g.7188-7192del5), c.640-16A>G (g.10115A>G), c.1000-22C>T (g.10956C>T). These mutations, located in promoter and intronic regulatory regions, have been observed in several patients with manifestations of FD. In our patient clinical picture showed a multisystemic involvement with early onset of symptoms, thus suggesting that these intronic mutations can be found even in patients with classical form of FD. BioMed Central 2012-06-08 /pmc/articles/PMC3425126/ /pubmed/22682330 http://dx.doi.org/10.1186/1471-2261-12-39 Text en Copyright ©2012 Pisani et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Case Report
Pisani, Antonio
Imbriaco, Massimo
Zizzo, Carmela
Albeggiani, Giuseppe
Colomba, Paolo
Alessandro, Riccardo
Iemolo, Francesco
Duro, Giovanni
A classical phenotype of Anderson-Fabry disease in a female patient with intronic mutations of the GLA gene: a case report
title A classical phenotype of Anderson-Fabry disease in a female patient with intronic mutations of the GLA gene: a case report
title_full A classical phenotype of Anderson-Fabry disease in a female patient with intronic mutations of the GLA gene: a case report
title_fullStr A classical phenotype of Anderson-Fabry disease in a female patient with intronic mutations of the GLA gene: a case report
title_full_unstemmed A classical phenotype of Anderson-Fabry disease in a female patient with intronic mutations of the GLA gene: a case report
title_short A classical phenotype of Anderson-Fabry disease in a female patient with intronic mutations of the GLA gene: a case report
title_sort classical phenotype of anderson-fabry disease in a female patient with intronic mutations of the gla gene: a case report
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3425126/
https://www.ncbi.nlm.nih.gov/pubmed/22682330
http://dx.doi.org/10.1186/1471-2261-12-39
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