Fanny Mochel, Domitille Gras, Marie-Pierre Luton, Manon Nizou, Donatella Giovannini, Caroline Delattre, Mélodie Aubart, Magalie Barth, Anne De Saint-Martin, Diane Doummar, Nouha Essid, Alexa Garros, Caroline Hachon Le Camus, Celia Hoebeke, Sylvie Nguyen The Tich, Maximilien Perivier, Serge Rivera, Anne Rolland, Agathe Roubertie, Catherine Sarret, Caroline Sevin, Dorothee Ville, Marc Sitbon, Jean-Marc Costa, Roser Pons, Angels Garcia-Cazorla, Sandrine Vuillaumier, Vincent Petit, Odile Boespflug-Tanguy, Darryl C. De Vivo, Isabelle An, Laurent Bailly, David Bendetowicz, Perrine Charles, Cécile Delorme, Sophie Demeret, Camille Giron, Solveig Heide, Anna Heinzmann, Mathilde Lalaude, Aurélie Méneret, Nicolas Mezouar, Marie-Lorraine Monin, Linda Mouthon, Emmanuel Roze, Clément Tarrano, Nicolas Villain, Elise Yazbeck, Stéphane Auvin, Lydie Da Costa, Blandine Dozières, Vincent des Portes, Zeynep Gokce-Samar, Eleni Panagiotakaki, Sabrine Souci, Joseph Toulouse, Céline Bellesme, Hélène Maurey, Lucie Salah, Thierry Billette De Villemeur, Pauline Garzon, Bénédicte Héron, Arnaud Isapof, Marie-Christine Nougues, Claudia Ravelli, Florence Renaldo, Diana Rodriguez, Stéphanie Valence, Marie-Thérèse Dangles, Pascale De Lonlay, Isabelle Desguerre, Chloé Durrleman, Marie Hully, Francesca Albertini, Aline Cano, Brigitte Chabrol, Julie Chavany, Elsa Kaphan, Stanislas Lagarde, Nathalie Villeneuve, Justine Avez-Couturier, Laurence Chaton, Jean-Christophe Cuvellier, Rabha Dehak, Florence Flamein Ballay, Valentine Floret, Ganaëlle Remérand, Marie-Thérèse Abi Warde, Mathieu Anheim, Yvan De Feraudy, Odile Gebus, Caroline Perriard, Marie-Aude Spitz, Mirna Khalil, Cécilia Marelli Tosi, Blanca Mercedes Alvarez, Pierre Meyer, Sarai Urtiaga Valle, Mathilde Canon, Christine Ioos, Caroline Espil, Marie Husson, Cyril Goizet, Vincent Michaud, Jean-Michel Pedespan, Léna Damaj, Sarah Hadjadj, Alinoë Lavillaureix, Jean-Marie Lepage, Mélissa Ugolin, Rachel Froget, Cécile Laroche, Claude Cancès, Yu Jin Salel, Agnès Viguier, Laure Mazzola, Laurine Perrin, Gérard Besson, Fanny Dubois, Elodie Lametery, Coralie Jacquet, Loïc De Pontual, Pierre Castelnau, Emmanuelle Lagrue, Marc Gibaud, Mondher Chouchane, Véronique Darmency, Clémence Fauconnier Fatus, Claire Bilbault, Anne Charlotte Cullier, Jacinthe Mekary, Jawida Touhami, Marie-Elodie Baer, Nadine Litou, Simon Samaan, Christophe Béesau, Floriane Bitaudeau, Christelle Cousin, Elodie Desport, Lynda Djouadi, Yasmine Hamadi, Emeline Lebreton, Sandra Moriceau

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 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 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 SLC2A1 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 SCL2A1 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.