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Title: | Frequency of Fabry disease in male and female haemodialysis patients in Spain |
Authors: | Gaspar, Paulo Herrera, Julio Rodrigues, Daniel Cerezo, Sebastian Delgado, Rodrigo Andrade, Carlos F Forascepi, Ramon Macias, Juan del Pino, Maria D Prados, Maria D de Alegria, de Pilar R Torres, Gerardo Vidau, Pedro Sa-Miranda, Maria C |
metadata.dc.contributor.authoraffiliation: | [Gaspar P; Rodrigues D; Sa-Miranda MC] Unidade de Biologia do Lisossoma e do Peroxissoma, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal. [Herrera J; Vidau P] Servicio de Nefrologia, Hospital Universitario Central de Asturias, Oviedo, Spain. [Cerezo S; Prados MD] Servicio de Nefrologia, Hospital Clínico San Cecilio, Granada, Spain. [Delgado R; Andrade CF] Servicio de Nefrologia, Hospital Virgen del Rocío, Sevilla, Spain. [Forascepi R] Servicio de Nefrologia, Hospital de Cabueñes, Gijon, Spain. [Macias J] Servicio de Nefrologia, Hospital Clínico de Salamanca, Salamanca, Spain. [del Pino MD] Servicio de Nefrologia, Hospital Torrecárdenas, Almeria, Spain. [de Alegria PR] Servicio de Nefrologia, Hospital de la Cruz Roja de Oviedo, Oviedo, Spain. [Torres G] Servicio de Nefrologia, Hospital General Yagüe, Burgos, Spain. |
Keywords: | Alelos;Amino Acid Substitution;Genotipo;Heterocigoto;Mediana Edad;Mutación;Fenotipo;Diálisis Renal;alfa-Galactosidasa;España;Femenino;Masculino;Adulto;Anciano de 80 o más años;Humanos |
metadata.dc.subject.mesh: | Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Alleles Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Mutagenesis::Amino Acid Substitution Medical Subject Headings::Diseases::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Brain Diseases, Metabolic::Brain Diseases, Metabolic, Inborn::Lysosomal Storage Diseases, Nervous System::Sphingolipidoses::Fabry Disease Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genotype Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genotype::Heterozygote Medical Subject Headings::Named Groups::Persons::Age Groups::Adult::Middle Aged Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Phenotype Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Renal Replacement Therapy::Renal Dialysis Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Glycoside Hydrolases::Galactosidases::alpha-Galactosidase Medical Subject Headings::Geographicals::Geographic Locations::Europe::Spain Medical Subject Headings::Named Groups::Persons::Age Groups::Adult::Aged::Aged, 80 and over Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans |
Issue Date: | 2010 |
Publisher: | BioMed Central |
Citation: | Gaspar P, Herrera J, Rodrigues D, Cerezo S, Delgado R, Andrade CF, et al. Frequency of Fabry disease in male and female haemodialysis patients in Spain. BMC Med Genet.[Internet]. 2010;11:19. |
Abstract: | BACKGROUND: Fabry disease (FD), an X-linked lysosomal storage disorder, is caused by a reduced activity of the lysosomal enzyme alpha-galactosidase A. The disorder ultimately leads to organ damage (including renal failure) in males and females. However, heterozygous females usually present a milder phenotype with a later onset and a slower progression. METHODS: A combined enzymatic and genetic strategy was used, measuring the activity of alpha-galactosidase A and genotyping the alpha-galactosidase A gene (GLA) in dried blood samples (DBS) of 911 patients undergoing haemodialysis in centers across Spain. RESULTS: GLA alterations were found in seven unrelated patients (4 males and 3 females). Two novel mutations (p.Gly346AlafsX347 and p.Val199GlyfsX203) were identified as well as a previously described mutation, R118C. The R118C mutation was present in 60% of unrelated patients with GLA causal mutations. The D313Y alteration, considered by some authors as a pseudo-deficiency allele, was also found in two out of seven patients. CONCLUSIONS: Excluding the controversial D313Y alteration, FD presents a frequency of one in 182 individuals (0.55%) within this population of males and females undergoing haemodialysis. Moreover, our findings suggest that a number of patients with unexplained and atypical symptoms of renal disease may have FD. Screening programmes for FD in populations of individuals presenting severe kidney dysfunction, cardiac alterations or cerebrovascular disease may lead to the diagnosis of FD in those patients, the study of their families and eventually the implementation of a specific therapy. |
metadata.dc.description.otherabstracts: | Enfermedad de Fabry (FD), un trastorno ligado al cromosoma X de almacenamiento lisosomal, es causada por una reducción de la actividad de la enzima lisosomal alfa-galactosidasa A. El desorden en última instancia, conduce a daños en los órganos (que incluyen insuficiencia renal) en hombres y mujeres. Sin embargo, las mujeres heterocigotas suelen presentar un fenotipo más leve, con un inicio más tardío y una progresión más lenta. MÉTODOS: Una estrategia combinada enzimática y genética se utilizó la medición de la actividad de la alfa-galactosidasa A y genotipo de la alfa-galactosidasa A gen (GLA) en muestras de sangre seca (DBS) de 911 pacientes sometidos a hemodiálisis en los centros de toda España. RESULTADOS: GLA se encontraron alteraciones en siete pacientes no relacionados (4 hombres y 3 mujeres). Dos nuevas mutaciones (p.Gly346AlafsX347 y p.Val199GlyfsX203) fueron identificados, así como una mutación se ha descrito anteriormente, R118C. La mutación R118C estuvo presente en el 60% de los pacientes no relacionados con mutaciones causales de GLA. La alteración D313Y, considerado por algunos autores como un alelo pseudo-deficiencia, también se encontró en dos de cada siete pacientes. CONCLUSIONES: Excluyendo la alteración D313Y polémica, DF presenta una frecuencia de uno en 182 individuos (0,55%) dentro de esta población de hombres y mujeres sometidos a hemodiálisis. Por otra parte, nuestros resultados sugieren que un número de pacientes con síntomas inexplicables y atípicos de la enfermedad renal puede tener FD. Los programas de detección de FD en las poblaciones de individuos que presentan una disfunción renal grave, alteraciones cardiacas o enfermedad cerebrovascular puede conducir al diagnóstico de la FD en los pacientes, el estudio de sus familias y, finalmente, la aplicación de una terapia específica. |
URI: | http://hdl.handle.net/10668/369 |
metadata.dc.relation.publisherversion: | http://www.biomedcentral.com/1471-2350/11/19/abstract |
metadata.dc.identifier.doi: | 10.1186/1471-2350-11-19 |
ISSN: | 1471-2350 (Online) |
Appears in Collections: | 01- Artículos - Complejo Hospitalario Torrecárdenas 01- Artículos - Hospital San Cecilio 01- Artículos - Hospital Virgen del Rocío |
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Gaspar_Frequency.pdf | Artículo publicado | 350,25 kB | Adobe PDF | View/Open |
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