Department of Pediatrics, Medical University of Graz, Graz, Austria.
Am J Kidney Dis. 2011 May;57(5):673-81. doi: 10.1053/j.ajkd.2010.10.046. Epub 2010 Dec 24.
Fabry disease is a treatable X-linked lysosomal storage disorder caused by alterations in the structural gene (GLA) of α-galactosidase A (AGAL), manifesting with cardiovascular and/or kidney disease and decreased life span. Although males as well as females can be affected, females cannot be identified using AGAL activity. We evaluated urinary total globotriaosylceramide (Gb3) and single N-acyl isoforms for the detection of Fabry disease in female patients with and without chronic kidney disease (CKD).
Diagnostic accuracy study.
SETTING & PARTICIPANTS: 28 untreated women with Fabry disease and 335 female outpatients without Fabry disease with (n = 213) and without CKD (n = 122).
Assessment of urinary Gb3 using electrospray ionization tandem mass spectrometry, including 6 N-acyl isoforms, total Gb3 related to urinary creatinine, and ratios of Gb3-24 to Gb3-18 and Gb3-24 to urinary AGAL.
Fabry disease, diagnosed by identification of known pathogenic GLA mutations in patients or their male relatives.
6 parameters (ratio of Gb3-24 to urinary AGAL activity; Gb3-24; ratio of Gb3-24 to Gb3-18; Gb3-22; Gb3-16; and total Gb3) were highly informative for the diagnosis of Fabry disease independent of the presence or absence of CKD (area under the receiver operating characteristic curve, 0.876-0.927; all P < 0.001).
Because of low signal-to-noise ratios, 15.8% of samples had to be excluded.
Total urinary Gb3 and Gb3 isoforms can be used for the diagnosis of Fabry disease in women.
法布里病是一种可治疗的 X 连锁溶酶体贮积症，由α-半乳糖苷酶 A（AGAL）的结构基因（GLA）改变引起，表现为心血管和/或肾脏疾病以及寿命缩短。尽管男性和女性都可能受到影响，但不能使用 AGAL 活性来识别女性。我们评估了尿总神经酰胺三己糖苷（Gb3）和单 N-酰基异构体，以检测有和无慢性肾脏病（CKD）的女性患者中的法布里病。
诊断准确性研究。
28 名未经治疗的法布里病女性患者和 335 名无法布里病的女性门诊患者，其中有（n = 213）和无 CKD（n = 122）。
采用电喷雾串联质谱法评估尿 Gb3，包括 6 种 N-酰基异构体、与尿肌酐相关的总 Gb3 以及 Gb3-24 与 Gb3-18 和 Gb3-24 与尿 AGAL 的比值。
通过鉴定患者或其男性亲属中已知的致病性 GLA 突变来诊断法布里病。
6 个参数（Gb3-24 与尿 AGAL 活性的比值；Gb3-24；Gb3-24 与 Gb3-18 的比值；Gb3-22；Gb3-16；和总 Gb3）在有无 CKD 的情况下，对法布里病的诊断均具有高度信息性（受试者工作特征曲线下面积，0.876-0.927；所有 P<0.001）。
由于信噪比低，15.8%的样本不得不被排除。
尿总 Gb3 和 Gb3 异构体可用于女性法布里病的诊断。
