Two-tier approach for the detection of alpha-galactosidase A deficiency in kidney transplant recipients.
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.
De Schoenmakere
Gert
G
Department of Nephrology, Ghent University Hospital, Ghent, Belgium. gdeschoenmakere@hhr.be
Poppe
Bruce
B
Wuyts
Birgitte
B
Claes
Kathleen
K
Cassiman
David
D
Maes
Bart
B
Verbeelen
Dierik
D
Vanholder
Raymond
R
Kuypers
Dirk R
DR
Lameire
Norbert
N
De Paepe
Anne
A
Terryn
Wim
W
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
D000519:alpha-Galactosidase