Genetic Screening of Anderson-Fabry Disease in Probands Referred From Multispecialty Clinics
| Autor: | Claudio Rapezzi, Eloisa Arbustini, Manuela Agozzino, Maurizio Melis, Filippo Mangione, Annarita Colucci, Alexandra Smirnova, Riccardo Borroni, Elena Biagini, M Molinaro, Jagat Narula, Maurizia Rasura, Valentina Favalli, Alessandra Serio, Nupoor Narula, Antonello Ganau, Daniela Concolino, Maria Teresa Di Mascio, Antonia Nucera, GianPietro Sechi, Clelia Caspani, Camilla Vassallo, Carlo Pellegrini, Eliana Disabella, Umberto Scoditti, Marilena Tagliani, Calogero Giordano, Pamela Cassini, Massimiliano Marini, Carmela Giorgianni, Elena Antoniazzi, Anna Scarabotto, Donata Guidetti, Takahide Kodama, Marina Diomedi, Michelangelo Mancuso, Danilo Toni, Marialuisa Zedde, Luigi Tavazzi, Maurizia Grasso, Laura Scelsi, Lorenzo Giuliani, Laura Fancellu, Stefania Piga, Monica Concardi, Stefano Ghio |
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| Přispěvatelé: | Favalli, Valentina, Disabella, Eliana, Molinaro, Mariadelfina, Tagliani, Marilena, Scarabotto, Anna, Serio, Alessandra, Grasso, Maurizia, Narula, Nupoor, Giorgianni, Carmela, Caspani, Clelia, Concardi, Monica, Agozzino, Manuela, Giordano, Calogero, Smirnova, Alexandra, Kodama, Takahide, Giuliani, Lorenzo, Antoniazzi, Elena, Borroni, Riccardo G, Vassallo, Camilla, Mangione, Filippo, Scelsi, Laura, Ghio, Stefano, Pellegrini, Carlo, Zedde, Marialuisa, Fancellu, Laura, Sechi, Gianpietro, Ganau, Antonello, Piga, Stefania, Colucci, Annarita, Concolino, Daniela, Di Mascio, Maria Teresa, Toni, Danilo, Diomedi, Marina, Rapezzi, Claudio, Biagini, Elena, Marini, MASSIMILIANO LUIGI IVO, Rasura, Maurizia, Melis, Maurizio, Nucera, Antonia, Guidetti, Donata, Mancuso, Michelangelo, Scoditti, Umberto, Cassini, Pamela, Narula, Jagat, Tavazzi, Luigi, Arbustini, Eloisa |
| Rok vydání: | 2016 |
| Předmět: |
Adult
Male Proband GLA MOGE(S) classification biochemical family screening multidisciplinary evaluation α-Gal Pediatrics medicine.medical_specialty Pathology Adolescent Disease 030204 cardiovascular system & hematology NO 03 medical and health sciences 0302 clinical medicine medicine Lysosomal storage disease Humans Genetic Testing Prospective Studies Child Prospective cohort study Genetic testing Alpha-galactosidase biology medicine.diagnostic_test business.industry Middle Aged medicine.disease Fabry disease Hospitals 3. Good health Anderson-Fabry Disease Settore MED/03 - Genetica Medica alpha-Galactosidase Mutation biology.protein Fabry Disease Medicine Female Settore MED/26 - Neurologia Cardiology and Cardiovascular Medicine business 030217 neurology & neurosurgery |
| Zdroj: | Journal of the American College of Cardiology. 68:1037-1050 |
| ISSN: | 0735-1097 |
| DOI: | 10.1016/j.jacc.2016.05.090 |
| Popis: | Anderson-Fabry disease (AFD) is a rare X-linked lysosomal storage disease, caused by defects of the alpha-galactosidase A (GLA) gene. AFD can affect the heart, brain, kidney, eye, skin, peripheral nerves, and gastrointestinal tract. Cardiology (hypertrophic cardiomyopathy), neurology (cryptogenic stroke), and nephrology (end-stage renal failure) screening studies suggest the prevalence of GLA variants is 0.62%, with diagnosis confirmation in 0.12%. OBJECTIVES: This study sought to expand screening from these settings to include ophthalmology, dermatology, gastroenterology, internal medicine, pediatrics, and medical genetics to increase diagnostic yield and comprehensively evaluate organ involvement in AFD patients. METHODS: In a 10-year prospective multidisciplinary, multicenter study, we expanded clinical, genetic, and biochemical screening to consecutive patients enrolled from all aforementioned clinical settings. We tested the GLA gene and α-galactosidase A activity in plasma and leukocytes. Inclusion criteria comprised phenotypical traits and absence of male-to-male transmission. Screening was extended to relatives of probands harboring GLA mutations. RESULTS: Of 2,034 probands fulfilling inclusion criteria, 37 (1.8%) were carriers of GLA mutations. Cascade family screening identified 60 affected relatives; clinical data were available for 4 affected obligate carriers. Activity of α-galactosidase A in plasma and leukocytes was diagnostic in male subjects, but not in female subjects. Of the 101 family members harboring mutations, 86 were affected, 10 were young healthy carriers, and 5 refused clinical evaluation. In the 86 patients, involved organs or organ systems included the heart (69%), peripheral nerves (46%), kidney (45%), eye (37%), brain (34%), skin (32%), gastrointestinal tract (31%), and auditory system (19%). Globotriaosylceramide accumulated in organ-specific and non-organ-specific cells in atypical and classic variants, respectively. CONCLUSIONS: Screening probands with clinically suspected AFD significantly increased diagnostic yield. The heart was the organ most commonly involved, independent of the clinical setting in which the patient was first evaluated. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. |
| Databáze: | OpenAIRE |
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