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

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; Dorothée 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

doi:10.1212/WNL.0000000000207296

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

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

Fanny Mochel, Domitille Gras, Marie-Pierre Luton, Manon Nizou, Donatella Giovannini, Caroline Delattre, Mélodie Aubart, Magalie Barth, Anne de Saint-Martin, Diane Doummar, …

Neurology, Vol.100(23), pp.e2360-e2373

06/06/2023

DOI: https://doi.org/10.1212/WNL.0000000000207296

PMCID: PMC10256121

PMID: 37076312

Abstract

Background and Objective 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. Methods 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. Results 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.

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Title: Prospective Multicenter Validation of a Simple Blood Test for the Diagnosis of Glut1 Deficiency Syndrome
Creators - without role: Fanny Mochel - Sorbonne Université
Domitille Gras - Université de Montpellier
Marie-Pierre Luton - Institut du Cerveau
Manon Nizou - Université de Montpellier
Donatella Giovannini - Université de Montpellier, Institut de Génétique Moléculaire de Montpellier - IGMM
Caroline Delattre - Centre National de la Recherche Scientifique
Mélodie Aubart - Université de Montpellier
Magalie Barth - CEA Paris-Saclay
Anne de Saint-Martin - Hôpital de Hautepierre [Strasbourg]
Diane Doummar - Sorbonne Université
Nouha Essid - Inserm
Alexa Garros - CEA Paris-Saclay
Caroline Hachon Le Camus - Université de Montpellier
Celia Hoebeke - Université de Montpellier
Sylvie Nguyen The Tich - Hôpital Roger Salengro
Maximilien Perivier - Inserm
Serge Rivera - Université de Montpellier
Anne Rolland - Commissariat à l'Énergie Atomique et aux Énergies Alternatives
Agathe Roubertie - Université de Montpellier, Institut des Neurosciences de Montpellier - INM
Catherine Sarret - Sorbonne Université
Caroline Sevin - Inserm
Dorothée Ville - Université de Montpellier
Marc Sitbon - Université de Montpellier, Institut de Génétique Moléculaire de Montpellier - IGMM
Jean-Marc Costa - Laboratoire CERBA [Saint Ouen l'Aumône]
Roser Pons - Inserm
Angels Garcia-Cazorla - Inserm
Sandrine Vuillaumier - Université de Montpellier
Vincent Petit - Commissariat à l'Énergie Atomique et aux Énergies Alternatives
Odile Boespflug-Tanguy - Sorbonne Université
Darryl C de Vivo - Sorbonne Université
Isabelle An - Charmo University
Laurent Bailly - Charmo University
David Bendetowicz - Charmo University
Perrine Charles - Charmo University
Cécile Delorme - Charmo University
Sophie Demeret - Charmo University
Camille Giron - Charmo University
Solveig Heide - Charmo University
Anna Heinzmann - Charmo University
Mathilde Lalaude - Charmo University
Aurélie Méneret - Charmo University
Nicolas Mezouar - Charmo University
Marie-Lorraine Monin - Charmo University
Linda Mouthon - Charmo University
Emmanuel Roze - Charmo University
Clément Tarrano - Charmo University
Nicolas Villain - Charmo University
Elise Yazbeck - Charmo University
Stéphane Auvin - Charmo University
Lydie Da Costa - Charmo University
Blandine Dozières - Charmo University
Vincent Des Portes - Charmo University
Zeynep Gokce-Samar - Charmo University
Eleni Panagiotakaki
Sabrine Souci
Joseph Toulouse
Céline Bellesme
Hélène Maurey
Lucie Salah
Thierry Billette de Villemeur - Charmo University
Pauline Garzon - Charmo University
Bénédicte Héron - Charmo University
Arnaud Isapof - Charmo University
Marie-Christine Nougues - Charmo University
Claudia Ravelli - Charmo University
Florence Renaldo - Charmo University
Diana Rodriguez - Charmo University
Stéphanie Valence - Charmo University
Marie-Thérèse Dangles
Pascale de Lonlay
Isabelle Desguerre
Chloé Durrleman
Marie Hully - Inserm
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 - Hôpital Robert-Debré
Caroline Perriard - Assistance Publique – Hôpitaux de Paris
Marie-Aude Spitz
Mirna Khalil
Cécilia Marelli Tosi
Blanca Mercedes Alvarez
Pierre Meyer - Assistance Publique – Hôpitaux de Paris
Sarai Urtiaga Valle
Mathilde Canon
Christine Ioos
Caroline Espil - Assistance Publique – Hôpitaux de Paris
Marie Husson - Inserm
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 - Inserm
Elodie Lametery - Hôpital Necker-Enfants Malades
Coralie Jacquet
Loïc de Pontual
Pierre Castelnau - Assistance Publique – Hôpitaux de Paris
Emmanuelle Lagrue
Marc Gibaud - Virbac
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 - Hôpital Necker-Enfants Malades
Lynda Djouadi
Yasmine Hamadi
Emeline Lebreton
Sandra Moriceau
Publication Details: Neurology, Vol.100(23), pp.e2360-e2373
Grant note: This study was supported by French Health Authorities, through the Forfait Innovation, and has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 806038.
Identifiers: 9940427409311
Academic Unit: Institut de Génétique Moléculaire de Montpellier - IGMM; Institut des Neurosciences de Montpellier - INM
Language: English
Resource Type: Journal article
Local Fields: hal-04347222