Evaluating the Performance of METAglut-1 in Patients Whose Clinical Presentation is Compatible with the Glucose Transporter-1 Deficiency Syndrome (GLUT-1 DS)

Objectives: The diagnosis of glucose transporter-1 deficiency syndrome (GLUT-1 DS) can be challenging due to the phenotypic heterogeneity among patients, coupled to confirmation that relies on the one hand on a measure of cerebral spinal fluid (CSF) glucose concentration typically reduced, but not always, and requires an invasive procedure. On the other hand, genetic analysis of the SLC2A1 gene can lead to results which are difficult to interpret.

Background: The METAglut-1 blood test was able to detect a significantly lower expression of GLUT-1 at the surface of red blood cells among 23 out of 30 patients tested who had been diagnosed with the disease. The current study will allow a large-scale evaluation of the test’s performance and has received a grant through the Forfait innovation scheme from the French Ministry of Health and the High Authority for Health (Haute Autorité de Santé, France).

Methods: When a patient presents clinical symptoms suggesting a GLUT-1 deficiency, a METAglut-1 test will be systematically performed blindly from the reference strategy consisting in the measure of CSF glucose concentration complemented genetic analysis. The study is multicentric and patients, children, and adults will be recruited in more than 40 centers all over France. The main goal will be to estimate the concordance between the METAglut-1 test and CSF glucose concentration among all patients with a diagnostic of certainty (either positive or negative) in the prospective cohort. Patients already diagnosed can be included in a retrospective arm to strengthen exploratory the data. A medical and economic analysis will be performed to evaluate the patients’ care pathway.

Conclusion: This study will allow to evaluate the diagnostic benefit of the METAglut-1 test and its place in the diagnostic strategy of the GLUT-1 deficiency syndrome. The confirmation of the high performance of the test will be very valuable as it only requires a simple venous blood test, no need for fasting, and is characterized by a quick turnaround time, to improve the early detection of patients which is of prime importance in this neurological pathology for which efficient therapies are available.