title: Frequency of Fabry disease in male and female haemodialysis patients in Spain.
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.
authors.affiliation: Unidade de Biologia do Lisossoma e do Peroxissoma, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
authors.forename: Paulo
authors.initials: P
authors.lastname: Gaspar
authors.forename: Julio
authors.initials: J
authors.lastname: Herrera
authors.forename: Daniel
authors.initials: D
authors.lastname: Rodrigues
authors.forename: Sebastián
authors.initials: S
authors.lastname: Cerezo
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Delgado
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Andrade
authors.forename: Ramón
authors.initials: R
authors.lastname: Forascepi
authors.forename: Juan
authors.initials: J
authors.lastname: Macias
authors.forename: Maria D
authors.initials: MD
authors.lastname: del Pino
authors.forename: Maria D
authors.initials: MD
authors.lastname: Prados
authors.forename: Pilar R
authors.initials: PR
authors.lastname: de Alegria
authors.forename: Gerardo
authors.initials: G
authors.lastname: Torres
authors.forename: Pedro
authors.initials: P
authors.lastname: Vidau
authors.forename: Maria C
authors.initials: MC
authors.lastname: Sá-Miranda
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D000483:Alleles; D019943:Amino Acid Substitution; D000795:Fabry Disease / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D006435:Renal Dialysis; D013030:Spain; D000519:alpha-Galactosidase / Q000235:genetics* / Q000378:metabolism
chemical_list: D000519:alpha-Galactosidase