Fabry disease: Detection of undiagnosed hemodialysis patients and identification of a "renal variant" phenotype
Fabry disease: Detection of undiagnosed hemodialysis patients and identification of a "renal variant" phenotype
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DOI：
10.1046/j.1523-1755.2003.00160.x
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发表时间：
2003-09-01
影响因子：
19.6
通讯作者：
Desnick, RJ
中科院分区：
文献类型：
--
作者：
Nakao, S;Kodama, C;Desnick, RJ
背景法布里病是由α-半乳糖苷酶A（α-Gal A）活性缺陷引起的X连锁隐性溶酶体贮积病。肾衰竭是一个主要的衰弱并发症在经典的影响男性。为了确定这种疾病是否在终末期肾病（ESRD）患者中诊断不足，确定了长期血液透析中未被识别的男性法布里病患者的频率。在514名连续接受血液透析的ESRD男性患者中测定血浆α-Gal A活性。对低α-Gal A活性的患者进行临床评估并测定其α-Gal A突变。514例血液透析患者中有6例（1.2%）具有低血浆α-Gal A活性和先前确定的（E66 Q、A97 V、M296 I）或新的（G373 D）错义突变。年龄在30 - 68岁之间，5例患者缺乏血管角化瘤、肢端感觉异常、多汗和眼部混浊的典型表现，而第6例患者缺乏血管角化瘤和眼部改变。5例有左心室肥厚（LVH）。法布里病的临床谱包括在没有典型症状的发展为ESRD的患者中的“肾变异”表型。接受血液透析或肾移植的受影响男性可以通过血浆α-Gal A测定容易地诊断。这些患者及其家庭成员可能受益于酶替代疗法，以治疗法布里病的晚期危及生命的心血管和脑血管并发症。
Background. Fabry disease is an X-linked recessive lysosomal storage disease resulting from deficient alpha-galactosidase A (alpha-Gal A) activity. Renal failure is a major debilitating complication in classically affected males. To determine if this disorder is underdiagnosed in patients with end-stage renal disease (ESRD), the frequency of unrecognized males with Fabry disease on chronic hemodialysis was determined.Methods. Plasma alpha-Gal A activity was measured in 514 consecutive males with ESRD on hemodialysis. Patients with low alpha-Gal A activity were evaluated clinically and their alpha-Gal A mutations were determined.Results. Six (1.2%) of 514 hemodialysis patients had low plasma alpha-Gal A activities and a previously identified (E66Q, A97V, M296I) or novel (G373D) missense mutation. At ages 30 to 68 years, five patients lacked the classic manifestations of angiokeratoma, acroparesthesias, hypohidrosis, and ocular opacities, while the sixth lacked angiokeratoma and ocular changes. Five had left ventricular hypertrophy (LVH).Conclusion. The clinical spectrum of Fabry disease includes a "renal variant" phenotype in patients without classic symptoms who develop ESRD. Affected males undergoing hemodialysis or renal transplantation can be readily diagnosed by plasma alpha-Gal A assays. These patients and their family members may benefit from enzyme replacement therapy for the later, life-threatening cardiovascular and cerebrovascular complications of Fabry disease.