De Schoenmakere Gert, Poppe Bruce, Wuyts Birgitte, Claes Kathleen, Cassiman David, Maes Bart, Verbeelen Dierik, Vanholder Raymond, Kuypers Dirk R, Lameire Norbert, De Paepe Anne, Terryn Wim
Department of Nephrology, Ghent University Hospital, Ghent, Belgium.
Nephrol Dial Transplant. 2008 Dec;23(12):4044-8. doi: 10.1093/ndt/gfn370. Epub 2008 Jul 2.
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.
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.
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.
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.
安德森-法布里病（AFD）是一种X连锁疾病，由溶酶体酶α-半乳糖苷酶缺乏引起。成年早期会出现多器官受累，重要器官受到影响，包括肾脏、大脑和心脏。然而，多项报告表明AFD的诊断不足。
我们采用两级方法对肾移植人群进行筛查。第一级是使用滤纸上的干血斑（DBFP）测定α-半乳糖苷酶A（AGALA）活性；在第二级中，对α-半乳糖苷酶水平最低的患者进一步进行GLA基因突变分析。
在2328例患者的数据库中，1233例符合纳入标准。最终，在获得知情同意后，对673例患者进行了筛查（54.5%，395例女性和278例男性）。DBFP分析得出AGALA的平均水平为2.63±2.48微摩尔/升/小时（第2.5百分位数和第97.5百分位数分别为0.0001和5.07微摩尔/升/小时）。11例患者接受了进一步的基因分析。在一名男性患者中鉴定出致病性错义突变p.Ala143Thr（c.427A>G）。
我们的结果表明，所提出的方法可以在迄今为止很少筛查的高危人群——肾移植患者中检测出AFD患者。我们得出结论，在高危人群中筛查AFD是一项具有成本效益、技术上可行且具有临床价值的目标。
