Frequency of Fabry disease in male and female haemodialysis patients in Spain.
Frequency of Fabry disease in male and female haemodialysis patients in Spain.
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DOI：
10.1186/1471-2350-11-19
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发表时间：
2010-02-01
影响因子：
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通讯作者：
Sá-Miranda MC
中科院分区：
文献类型：
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作者：
Gaspar P;Herrera J;Rodrigues D;Cerezo S;Delgado R;Andrade CF;Forascepi R;Macias J;del Pino MD;Prados MD;de Alegria PR;Torres G;Vidau P;Sá-Miranda MC
法布里病(FD)是一种X连锁的溶酶体储存障碍，由溶酶体酶α-半乳糖苷酶A活性降低引起，最终导致男性和女性的器官损害(包括肾功能衰竭)。然而，杂合子女性通常表现出较温和的表型，发病较晚，进展较慢。采用酶和遗传相结合的策略，检测了西班牙各地911名中心血液透析患者的干血样本中α-半乳糖苷酶A的活性，并对α-半乳糖苷酶A基因(Gla)进行了基因分型。在7名无关患者中发现GLA改变(4名男性和3名女性)。鉴定出两个新的突变(p.Gly346AlafsX347和p.Val199GlyfsX203)以及一个先前描述的突变R118C。R118C突变存在于60%无血缘关系的GLA因果突变患者中。D313Y改变被一些作者认为是一种假性缺乏等位基因，在7名患者中也有2名被发现。排除有争议的D313Y改变，在接受血液透析的男性和女性中，FD的发生率为每182人中就有一人(0.55%)。此外，我们的研究结果表明，一些有不明原因和不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进行FD筛查计划，可能会导致对这些患者的FD进行诊断，对他们的家人进行研究，并最终实施特定的治疗方法。
Fabry disease (FD), an X-linked lysosomal storage disorder, is caused by a reduced activity of the lysosomal enzyme α-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 α-galactosidase A and genotyping the α-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.