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 a determination of alphagalactosidase
A activity (AGALA) 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 2,328 patients, 1,233
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 _mol/L/h (2.5 and 97.5 percentile were 0.0001 and 5.07 _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.
Key words
Anderson-Fabry disease. Transplantation. Screening. Alpha-galactosidase.