Two-tier approach for the detection of alpha-galactosidase A deficiency in a predominantly female haemodialysis population.
BACKGROUND
Fabry's disease (AFD) is an X-linked lysosomal storage disease, resulting from a deficiency in alpha-galactosidase A (AGALA). Untreated, this leads to precocious failure of vital organ function and death. As enzyme replacement therapy is available, it is of vital importance that affected individuals can be traced.


METHODS
We set up a screening in the Flemish haemodialysis population using a two-tier approach. The first tier was a determination of alpha-galactosidase A activity using a dried blood spot on filter paper, in the second tier, patients with the lowest alpha-galactosidase levels were further subjected to mutation analysis of the GLA gene.


RESULTS
1284 patients (1047 women, 237 men) were evaluated for inclusion, eliminating patients with definite renal diagnoses. Total 922 patients (71.8 %) were screened (742 women, 180 men). Fifty seven patients were subjected to further genetic analysis. Three GLA mutation carriers were identified: two apparently nonrelated female patients carry the missense mutation p.Ala143Thr (c.427G > A), a missense mutation p.Trp236Arg (c.706T > C) was identified in a man. While the male patient had been clinically diagnosed with AFD, the female patients had remained unrecognized. Additional family based screening resulted in the identification of nine mutation carriers (four males and five females).


CONCLUSIONS
We demonstrated that the prevalence of GLA mutation carriers in our haemodialysis population is 0.3%. Our results show that the proposed approach accurately detects AFD patients. We conclude that screening for AFD in high risk populations is a cost-effective, technically feasible and clinically valuable objective.
Terryn
Wim
W
Department of Nephrology, Ghent University Hospital, Ghent, Belgium.
Poppe
Bruce
B
Wuyts
Birgitte
B
Claes
Kathleen
K
Maes
Bart
B
Verbeelen
Dierik
D
Vanholder
Raymond
R
De Boeck
Koen
K
Lameire
Norbert
N
De Paepe
Anne
A
De Schoenmakere
Gert
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis / Q000379:methods; D000795:Fabry Disease / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D006435:Renal Dialysis; D012737:Sex Factors