NDT Advance Access published online on July 2, 2008
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfn370
Two-tier approach for the detection of alpha-galactosidase A deficiency in kidney transplant recipients
1 Department of Nephrology, Ghent University Hospital, Ghent 2 Department of Nephrology and Internal Medicine, Heilig Hart Hospital, Roeselare 3 Center for Medical Genetics, Ghent University Hospital, Ghent 4 Department of Clinical Biology, Ghent University Hospital, Ghent 5 Metabolic Center, University Hospitals Leuven, University of Leuven 6 Representative of NBVN (Nederlandstalige Belgische Vereniging voor Nefrologie) 7 Department of Nephrology, Universitair ziekenhuis Brussel, Brussels 8 Department of Nephrology and Renal Transplantation, University Hospital Gasthuisberg, Leuven 9 Department of Nephrology and Internal Medicine, Regional Hospital Jan Yperman, Ypres, Belgium
Correspondence and offprint requests to: Gert De Schoenmakere, Department of Nephrology and Internal Medicine, Heilig Hartziekenhuis Roeselare, B-8800 Roeselare, Belgium. Tel: +32-51-23-74-95; Fax: +32-51-23-74-95; E-mail: gdeschoenmakere{at}hhr.be
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Abstract |
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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 µmol/L/h (2.5 and 97.5 percentile were 0.0001 and 5.07 µmol/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.
Keywords: alpha-galactosidase; Anderson–Fabry disease; screening; transplantation
* The authors contributed equally to the study.
Received for publication: 3. 2.08
Accepted in revised form: 10. 6.08