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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2012
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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. |
format | Online Article Text |
id | pubmed-3425126 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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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