title: Two-tier approach for the detection of alpha-galactosidase A deficiency in kidney transplant recipients.
abstract: BACKGROUND
  Anderson-Fabry disease (AFD) is an X-linked condition originating from a deficiency in alpha-galactosidase, a lysosomal enzyme. Multi-organ involvement ensues in early adulthood and vital organs are affected: the kidneys, brain, heart. Several reports however suggest that AFD is underdiagnosed.
  
  
  METHODS
  We screened a kidney transplant population using a two-tier approach. The first tier was the determination of alpha-galactosidase A (AGALA) activity using a dried blood spot on filter paper (DBFP); in the second tier, patients with the lowest alpha-galactosidase levels were further subjected to mutation analysis of the GLA gene.
  
  
  RESULTS
  From the database of 2328 patients, 1233 subjects met the inclusion criteria. Finally, after informed consent, 673 patients were screened (54.5%-395 women and 278 men). DBFP analysis resulted in a mean AGALA of 2.63 +/- 2.48 micromol/L/h (2.5 and 97.5 percentile were 0.0001 and 5.07 micromol/L/h, respectively). Eleven patients were subjected to further genetic analysis. In a male patient a pathogenic missense mutation p.Ala143Thr (c.427A>G) was identified.
  
  
  CONCLUSIONS
  Our results show that the proposed approach can detect AFD patients in a until now seldomly screened high-risk group: kidney transplant patients. We conclude that screening for AFD in high-risk populations is a cost-effective, technically feasible and clinically valuable objective.
authors.affiliation: Department of Nephrology, Ghent University Hospital, Ghent, Belgium. gdeschoenmakere@hhr.be
authors.forename: Gert
authors.initials: G
authors.lastname: De Schoenmakere
authors.forename: Bruce
authors.initials: B
authors.lastname: Poppe
authors.forename: Birgitte
authors.initials: B
authors.lastname: Wuyts
authors.forename: Kathleen
authors.initials: K
authors.lastname: Claes
authors.forename: David
authors.initials: D
authors.lastname: Cassiman
authors.forename: Bart
authors.initials: B
authors.lastname: Maes
authors.forename: Dierik
authors.initials: D
authors.lastname: Verbeelen
authors.forename: Raymond
authors.initials: R
authors.lastname: Vanholder
authors.forename: Dirk R
authors.initials: DR
authors.lastname: Kuypers
authors.forename: Norbert
authors.initials: N
authors.lastname: Lameire
authors.forename: Anne
authors.initials: A
authors.lastname: De Paepe
authors.forename: Wim
authors.initials: W
authors.lastname: Terryn
mesh_terms: D000328:Adult; D000368:Aged; D002648:Child; D004252:DNA Mutational Analysis; D000795:Fabry Disease / Q000150:complications / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D006801:Humans; D007676:Kidney Failure, Chronic / Q000201:enzymology / Q000209:etiology / Q000235:genetics; D016030:Kidney Transplantation; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D055815:Young Adult; D000519:alpha-Galactosidase / Q000235:genetics
chemical_list: D000519:alpha-Galactosidase