Two-tier approach for the detection of alpha-galactosidase A deficiency in kidney transplant recipients.
Schoenmakere, Gert De 1,2,*; Poppe, Bruce 3,*; Wuyts, Birgitte 4; Claes, Kathleen 3; Cassiman, David 5; Maes, Bart 6,2; Verbeelen, Dierik 6,7; Vanholder, Raymond 1; Kuypers, Dirk R. 8; Lameire, Norbert 1; De Paepe, Anne 3; Terryn, Wim 1,9,*
[Article]
Nephrology Dialysis Transplantation.
23(12):4044-4048, December 2008.
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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 [mu]mol/L/h (2.5 and 97.5 percentile were 0.0001 and 5.07 [mu]mol/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.
(C) European Renal Association - European Dialysis and Transplant Association 2008. Published by Oxford University Press. All rights reserved.