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Broad spectrum of Fabry disease manifestation in an extended Spanish family with a new deletion in the GLA gene
BACKGROUND: Fabry disease (FD) is an X-linked inherited disease based on the absence or reduction of lysosomal-galactosidase (Gla) activity. The enzymatic defect results in progressive impairment of cerebrovascular, renal and cardiac function. Normally, female heterozygote mutation carriers are less...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4432423/ https://www.ncbi.nlm.nih.gov/pubmed/26019814 http://dx.doi.org/10.1093/ckj/sfs115 |
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author | Lukas, Jan Torras, Joan Navarro, Itziar Giese, Anne-Katrin Böttcher, Tobias Mascher, Hermann Lackner, Karl J. Fauler, Guenter Paschke, Eduard Cruzado, Josep M. Dudesek, Ales Wittstock, Matthias Meyer, Wolfgang Rolfs, Arndt |
author_facet | Lukas, Jan Torras, Joan Navarro, Itziar Giese, Anne-Katrin Böttcher, Tobias Mascher, Hermann Lackner, Karl J. Fauler, Guenter Paschke, Eduard Cruzado, Josep M. Dudesek, Ales Wittstock, Matthias Meyer, Wolfgang Rolfs, Arndt |
author_sort | Lukas, Jan |
collection | PubMed |
description | BACKGROUND: Fabry disease (FD) is an X-linked inherited disease based on the absence or reduction of lysosomal-galactosidase (Gla) activity. The enzymatic defect results in progressive impairment of cerebrovascular, renal and cardiac function. Normally, female heterozygote mutation carriers are less strongly affected than male hemizygotes aggravating disease diagnosis. METHOD: Close examination of the patients by renal biopsy, echo- and electrocardiography and MRI. Blood work and subsequent DNA analysis were carried out utilizing approved protocols for PCR and Sequencing. MLPA analysis was done to unveil deletions within the GLA gene locus. Quantitative detection of Glycolipids in patient plasma and urine were carried out using HPLC/MS-MS and ESI-MS. RESULTS: In the presented case, a female index patient led to the examination of three generations of a Spanish family. She presented with severe oto-cochlear symptoms and covert renal and cardiac involvement. While conventional sequencing failed to detect a causative mutation, MLPA analysis revealed a deletion within the GLA gene locus, which we were able to map to a region spanning exon 2 and adjacent intronic parts. The analysis of different biomarkers revealed elevated lyso-Gb3 levels in all affected family members. CONCLUSION: Our findings highlight the broad intrafamilial spectrum of symptoms of FD and emphasise the need to use MLPA screening in symptomatic females without conclusive sequencing result. Finally, plasma lyso-Gb3 proved to be a reliable biomarker for the diagnosis of FD. |
format | Online Article Text |
id | pubmed-4432423 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-44324232015-05-27 Broad spectrum of Fabry disease manifestation in an extended Spanish family with a new deletion in the GLA gene Lukas, Jan Torras, Joan Navarro, Itziar Giese, Anne-Katrin Böttcher, Tobias Mascher, Hermann Lackner, Karl J. Fauler, Guenter Paschke, Eduard Cruzado, Josep M. Dudesek, Ales Wittstock, Matthias Meyer, Wolfgang Rolfs, Arndt Clin Kidney J Original Contributions BACKGROUND: Fabry disease (FD) is an X-linked inherited disease based on the absence or reduction of lysosomal-galactosidase (Gla) activity. The enzymatic defect results in progressive impairment of cerebrovascular, renal and cardiac function. Normally, female heterozygote mutation carriers are less strongly affected than male hemizygotes aggravating disease diagnosis. METHOD: Close examination of the patients by renal biopsy, echo- and electrocardiography and MRI. Blood work and subsequent DNA analysis were carried out utilizing approved protocols for PCR and Sequencing. MLPA analysis was done to unveil deletions within the GLA gene locus. Quantitative detection of Glycolipids in patient plasma and urine were carried out using HPLC/MS-MS and ESI-MS. RESULTS: In the presented case, a female index patient led to the examination of three generations of a Spanish family. She presented with severe oto-cochlear symptoms and covert renal and cardiac involvement. While conventional sequencing failed to detect a causative mutation, MLPA analysis revealed a deletion within the GLA gene locus, which we were able to map to a region spanning exon 2 and adjacent intronic parts. The analysis of different biomarkers revealed elevated lyso-Gb3 levels in all affected family members. CONCLUSION: Our findings highlight the broad intrafamilial spectrum of symptoms of FD and emphasise the need to use MLPA screening in symptomatic females without conclusive sequencing result. Finally, plasma lyso-Gb3 proved to be a reliable biomarker for the diagnosis of FD. Oxford University Press 2012-10 /pmc/articles/PMC4432423/ /pubmed/26019814 http://dx.doi.org/10.1093/ckj/sfs115 Text en © The Author 2012. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For permissions, please email: journals.permissions@oup.com http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Original Contributions Lukas, Jan Torras, Joan Navarro, Itziar Giese, Anne-Katrin Böttcher, Tobias Mascher, Hermann Lackner, Karl J. Fauler, Guenter Paschke, Eduard Cruzado, Josep M. Dudesek, Ales Wittstock, Matthias Meyer, Wolfgang Rolfs, Arndt Broad spectrum of Fabry disease manifestation in an extended Spanish family with a new deletion in the GLA gene |
title | Broad spectrum of Fabry disease manifestation in an extended Spanish family with a new deletion in the GLA gene |
title_full | Broad spectrum of Fabry disease manifestation in an extended Spanish family with a new deletion in the GLA gene |
title_fullStr | Broad spectrum of Fabry disease manifestation in an extended Spanish family with a new deletion in the GLA gene |
title_full_unstemmed | Broad spectrum of Fabry disease manifestation in an extended Spanish family with a new deletion in the GLA gene |
title_short | Broad spectrum of Fabry disease manifestation in an extended Spanish family with a new deletion in the GLA gene |
title_sort | broad spectrum of fabry disease manifestation in an extended spanish family with a new deletion in the gla gene |
topic | Original Contributions |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4432423/ https://www.ncbi.nlm.nih.gov/pubmed/26019814 http://dx.doi.org/10.1093/ckj/sfs115 |
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