Prospective Multicenter Validation of a Simple Blood Test for the Diagnosis of Glut1 Deficiency Syndrome.

ObjectiveGLUT1 deficiency syndrome (Glut1DS) is a treatable neurometabolic disease that causes a wide range of neurological symptoms in children and adults. However, its diagnosis relies on an invasive test, i.e., a lumbar puncture (LP) to measure glycorrhachia, and, sometimes complex, molecular analyses of the 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 at the erythrocyte surface.MethodsWe performed a multicenter validation study in France, involving 33 centers. We studied two patient cohorts: a prospective cohort, consisting of patients with a clinical suspicion of Glut1DS explored through the reference strategy, i.e., LP and analyses of the gene; a retrospective cohort that included patients previously diagnosed with Glut1DS. All patients were blind-tested with METAglut1™.ResultsWe 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 mosaicism and variants of unknown significance.InterpretationMETAglut1™ is an easily performed, robust and non-invasive diagnostic test for the diagnosis of Glut1DS, which allows a wide screening of children and adults, including those with atypical forms of this treatable condition.Classification of EvidenceThis study provides class I evidence that a positive METAglut1™ test accurately distinguishes patients with suspected GLUT1 deficiency syndrome from other neurological syndromes as compared to invasive and genetic testing.