Non-invasive high-risk screening for Fabry disease hemizygotes and heterozygotes
Non-invasive high-risk screening for Fabry disease hemizygotes and heterozygotes
复制标题
DOI：
10.1007/s00467-008-0846-6
复制
发表时间：
2008-09-01
影响因子：
3
通讯作者：
Owada, Misao
中科院分区：
文献类型：
--
作者：
Kitagawa, Teruo;Suzuki, Ken;Owada, Misao
筛查法布里病（FD）的最合适时间是学龄期。为此，我们开发了使用酶联免疫吸附测定 (ELISA) 测量尿 α-半乳糖苷酶 A (α-gal A) 蛋白的非侵入性方法，以及使用串联质谱 (MS/MS) 测量尿三酰神经酰胺 (GL-3) 的非侵入性方法。我们在先前诊断的 FD 半合子和杂合子以及对照者的尿液中测量了这两种生物标志物。仅通过任一方法即可将所有经典 FD 半合子与对照清楚地区分开来，并且结合两种检测方法可产生 96% 的杂合子检测灵敏度。为了评估这些方法在筛查 FD 高风险学童和成人方面的效用，进行了一项试点研究。为了区分 FD 和 432 个对照，α-gal A 蛋白和 GL-3 的截止值分别设置为对照的第 5 个和第 95 个百分位值。在高危患者中，测量结果超过了男性和女性受试者生物标志物的临界值，是法布里半合子和杂合子的有力指标。然而，我们建议，如果第一次测量结果仅超过其中一个生物标志物的临界值，则应要求另一份尿液样本重新检测以确认结果。
The most appropriate time for screening for Fabry disease (FD) is school age. For this reason, we developed non-invasive methods for measuring urinary alpha-galactosidase A (alpha-gal A) protein, using enzyme-linked immunosorbent assay (ELISA), and for globotriaosylceramide (GL-3), using tandem mass spectrometry (MS/MS). We measured these two biomarkers in the urine of previously diagnosed FD hemizygotes and heterozygotes, and in controls. All the classic FD hemizygotes were clearly distinguished from controls by either method alone, and combining the two assays produced 96% sensitivity for detecting heterozygotes. To assess the utility of these methods for screening school children and adults at high risk of FD, a pilot study was conducted. To distinguish FD from 432 controls, cut-off values for alpha-gal A protein and GL-3 were set at the 5th and 95th centile values of the controls, respectively. Among the high-risk patients, the measurements exceeded the cut-off values for both biomarkers in male and female subjects and were strong indicators for Fabry hemizygotes and heterozygotes. However, we recommend that if the results of the first measurements exceed the cut-off values for only one of these biomarkers, another urine sample should be requested for re-assay to confirm the result.