NDT Advance Access originally published online on September 5, 2007
Nephrology Dialysis Transplantation 2008 23(1):294-300; doi:10.1093/ndt/gfm532
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Two-tier approach for the detection of alpha-galactosidase A deficiency in a predominantly female haemodialysis population
1Department of Nephrology, Ghent University Hospital, Ghent, 2Department of Nephrology and Internal Medicine, Regional Hospital Jan Yperman, Ypres, Belgium, 3Centre for Medical Genetics, 4Department of Clinical Biology, Ghent University Hospital, Ghent, 5Representative of NBVN (Nederlandstalige Belgische Vereniging voor Nefrologie), 6Department of Nephrology and Internal Medicine, Heilig Hart Hospital, Roeselare, 7Department of Nephrology, University Hospital Brussels, Brussels and 8Department of Nephrology, ZNA Middelheim, Antwerp, Belgium
Correspondence to: Gert De Schoenmakere, MD, Department of Nephrology and Internal Medicine, Heilig Hartziekenhuis Roeselare, B-8800 Roeselare, Belgium. Email: gdeschoenmakere{at}hhr.be
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Abstract |
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Introduction. 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.
Materials and 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).
Discussion. 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.
Keywords: alpha galactosidase; Fabry's disease; female; haemodialysis; screening
*These authors contributed equally to this work.
Received for publication: 8. 1.07
Accepted in revised form: 11. 7.07
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