Unidade de Biologia do Lisossoma e do Peroxissoma, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
BMC Med Genet. 2010 Feb 1;11:19. doi: 10.1186/1471-2350-11-19.
Fabry disease (FD), an X-linked lysosomal storage disorder, is caused by a reduced activity of the lysosomal enzyme alpha-galactosidase A. The disorder ultimately leads to organ damage (including renal failure) in males and females. However, heterozygous females usually present a milder phenotype with a later onset and a slower progression.
A combined enzymatic and genetic strategy was used, measuring the activity of alpha-galactosidase A and genotyping the alpha-galactosidase A gene (GLA) in dried blood samples (DBS) of 911 patients undergoing haemodialysis in centers across Spain.
GLA alterations were found in seven unrelated patients (4 males and 3 females). Two novel mutations (p.Gly346AlafsX347 and p.Val199GlyfsX203) were identified as well as a previously described mutation, R118C. The R118C mutation was present in 60% of unrelated patients with GLA causal mutations. The D313Y alteration, considered by some authors as a pseudo-deficiency allele, was also found in two out of seven patients.
Excluding the controversial D313Y alteration, FD presents a frequency of one in 182 individuals (0.55%) within this population of males and females undergoing haemodialysis. Moreover, our findings suggest that a number of patients with unexplained and atypical symptoms of renal disease may have FD. Screening programmes for FD in populations of individuals presenting severe kidney dysfunction, cardiac alterations or cerebrovascular disease may lead to the diagnosis of FD in those patients, the study of their families and eventually the implementation of a specific therapy.
法布瑞病（Fabry disease，FD）是一种 X 连锁溶酶体贮积症，由溶酶体酶α-半乳糖苷酶 A 的活性降低引起。该疾病最终会导致男性和女性的器官损伤（包括肾衰竭）。然而，杂合子女性通常表现出较轻的表型，发病较晚，进展较慢。
采用酶学和遗传学联合策略，在西班牙各地中心接受血液透析的 911 例患者的干血斑（DBS）中测量α-半乳糖苷酶 A 的活性，并对α-半乳糖苷酶 A 基因（GLA）进行基因分型。
在 7 名无亲缘关系的患者（4 名男性和 3 名女性）中发现了 GLA 改变。发现了两种新的突变（p.Gly346AlafsX347 和 p.Val199GlyfsX203）以及先前描述的突变 R118C。R118C 突变存在于 60%的无亲缘关系的 GLA 致病突变患者中。一些作者认为 D313Y 改变是一种伪缺陷等位基因，在 7 名患者中的 2 名中也发现了这种改变。
排除有争议的 D313Y 改变，在接受血液透析的男性和女性人群中，FD 的发病率为每 182 人中有 1 人（0.55%）。此外，我们的研究结果表明，一些具有不明原因和非典型肾脏疾病症状的患者可能患有 FD。在出现严重肾功能障碍、心脏改变或脑血管疾病的人群中开展 FD 筛查计划可能会在这些患者中诊断出 FD，研究他们的家族，并最终实施特定的治疗。
