PDF(Pubmed)
Abstract：
GLUT1 deficiency syndrome (Glut1DS) is a treatable neurometabolic disease that causes a wide range of neurologic symptoms in children and adults. However, its diagnosis relies on an invasive test, that is, a lumbar puncture (LP) to measure glycorrhachia, and sometimes complex molecular analyses of the SLC2A1 gene. This procedure limits the number of patients able to receive the standard of care. We wished to validate the diagnostic performance of METAglut1, a simple blood test that quantifies GLUT1 on the erythrocyte surface.
We performed a multicenter validation study in France, involving 33 centers. We studied 2 patient cohorts: a prospective cohort consisting of patients with a clinical suspicion of Glut1DS explored through the reference strategy, that is, LP and analyses of the SLC2A1 gene, and a retrospective cohort that included patients previously diagnosed with Glut1DS. All patients were blind-tested with METAglut1.
We analyzed 428 patients in the prospective cohort, including 15 patients newly diagnosed with Glut1DS, and 67 patients in the retrospective cohort. METAglut1 was 80% sensitive and >99% specific for the diagnosis of Glut1DS. Concordance analyses showed a substantial agreement between METAglut1 and glycorrhachia. In the prospective cohort, the positive predictive value of METAglut1 was slightly higher than that of glycorrhachia. METAglut1 succeeded to identify patients with Glut1DS with SCL2A1 mosaicism and variants of unknown significance.
METAglut1 is an easily performed, robust, and noninvasive diagnostic test for the diagnosis of Glut1DS, which allows wide screening of children and adults, including those with atypical forms of this treatable condition.
This study provides Class I evidence that a positive METAglut1 test accurately distinguishes patients with suspected GLUT1 deficiency syndrome from other neurologic syndromes as compared with invasive and genetic testing.
We performed a multicenter validation study in France, involving 33 centers. We studied 2 patient cohorts: a prospective cohort consisting of patients with a clinical suspicion of Glut1DS explored through the reference strategy, that is, LP and analyses of the SLC2A1 gene, and a retrospective cohort that included patients previously diagnosed with Glut1DS. All patients were blind-tested with METAglut1.
We analyzed 428 patients in the prospective cohort, including 15 patients newly diagnosed with Glut1DS, and 67 patients in the retrospective cohort. METAglut1 was 80% sensitive and >99% specific for the diagnosis of Glut1DS. Concordance analyses showed a substantial agreement between METAglut1 and glycorrhachia. In the prospective cohort, the positive predictive value of METAglut1 was slightly higher than that of glycorrhachia. METAglut1 succeeded to identify patients with Glut1DS with SCL2A1 mosaicism and variants of unknown significance.
METAglut1 is an easily performed, robust, and noninvasive diagnostic test for the diagnosis of Glut1DS, which allows wide screening of children and adults, including those with atypical forms of this treatable condition.
This study provides Class I evidence that a positive METAglut1 test accurately distinguishes patients with suspected GLUT1 deficiency syndrome from other neurologic syndromes as compared with invasive and genetic testing.
摘要：
目的GLUT1缺乏综合征（Glut1DS）是一种可治疗的神经代谢疾病，可在儿童和成人中引起广泛的神经系统症状。然而,它的诊断依赖于侵入性测试，即，腰椎穿刺（LP）来测量血糖，and,有时复杂，SLC2A1基因的分子分析。该程序限制了能够接受标准护理的患者数量。我们希望验证METAglut1™的诊断性能，对红细胞表面GLUT1进行定量的简单血液检测。方法我们在法国进行了一项多中心验证研究，涉及33个中心。我们研究了两个患者队列：前瞻性队列，由通过参考策略探索的临床怀疑Glut1DS的患者组成，即，LP和SLC2A1基因分析；一项回顾性队列，包括先前诊断为Glut1DS的患者。所有患者都用METAglut1™进行盲测试。结果我们分析了前瞻性队列中的428例患者，包括15例新诊断为Glut1DS的患者，回顾性队列中67例患者。METATAgl1™对Glut1DS的诊断具有80%的敏感性和>99%的特异性。一致性分析显示METATAglut1™和glycachina之间的基本一致。在前瞻性队列中，METAglut1™的阳性预测值略高于糖臂.METAglut1™成功地鉴定出具有SCL2A1镶嵌性和未知意义的变体的Glut1DS患者。InterpretationMETAglut1™是一个容易执行，用于诊断Glut1DS的稳健和非侵入性诊断测试，可以对儿童和成人进行广泛的筛查，包括那些非典型形式的这种可治疗的疾病。证据分类本研究提供了I类证据，即与侵入性和遗传测试相比，阳性METAglut1™测试可将疑似GLUT1缺乏综合征的患者与其他神经系统综合征准确区分开来。
