Two-tier approach for the detection of alpha-galactosidase A deficiency in kidney transplant recipients

Nephrol Dial Transplant. 2008 Dec;23(12):4044-8. doi: 10.1093/ndt/gfn370. Epub 2008 Jul 2.


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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Child
  • DNA Mutational Analysis
  • Fabry Disease / complications
  • Fabry Disease / diagnosis*
  • Fabry Disease / enzymology
  • Fabry Disease / genetics
  • Female
  • Genetic Testing
  • Humans
  • Kidney Failure, Chronic / enzymology
  • Kidney Failure, Chronic / etiology
  • Kidney Failure, Chronic / genetics
  • Kidney Transplantation*
  • Male
  • Mutation, Missense
  • Pedigree
  • Young Adult
  • alpha-Galactosidase / genetics


  • alpha-Galactosidase