New Blood Test Can Diagnose GLUT1 Deficiency Syndrome

A new blood test (METAglut1) successfully diagnosed patients with GLUT1 deficiency syndrome (Glut1DS), a neurometabolic disease that causes neurological symptoms, including seizures, in children and adults, according to a validation study published in Neurology.

“Glut1DS is an urgent diagnosis for patients, not to miss critical time where early treatments can be initiated to support brain development and function. To this end, we suggest to perform METAglut1 in any patient, after the age of 3 months…. Given the current estimated prevalence of Glut1DS, the availability of a simple blood test is a major milestone for patients with Glut1DS because their diagnosis and treatment will occur much faster,” recommended the authors.

GLUT1 deficiency syndrome is a neurometabolic disease that causes neurological symptoms, including seizures, in children and adults.

Glut1DS is a treatable, disabling, and rare disease caused by impaired glucose transport across the blood-brain barrier and into glial cells because of variants in the SLC2A1 gene, which encodes the glucose transporter GLUT1. Dysfunction of GLUT1 limits glucose availability in the brain and contributes to brain energy deficiency, potentially leading to epilepsy, permanent motor disorders, paroxysmal movement disorders, and cognitive impairment.

The condition is typically diagnosed using genetic testing involving a lumbar puncture to measure glyborrhachia as well as complex molecular analysis of the SLC2A1 gene. The invasive nature of these analyses can limit the number of patients able to receive the standard of care, revealing an unmet need for less invasive and more accessible diagnostic tests.

“Easy access to a blood biomarker for the early and fast diagnosis of Glut1DS could be determinant for patient outcome and of a major economic effect because earlier treatment is associated with greater patient’s prognosis,” the authors wrote.

The METAglut1 test can allow for early and quick diagnosis of Glut1DS. The test uses a simple blood draw and does not require patients to fast the night before. Although a pilot analyses have shown the test to have a high sensitivity for Glut1DS, the researchers set out to assess the diagnostic performance to METAglut1 in a multicenter validation study concerning 33 French facilities.

The researchers looked at 2 patient cohorts: the first included patients with a clinical suspicion of Glut1DS (prospective cohort; n = 428) and the second included patients previously diagnoses with the condition (retrospective cohort; n = 67). All patients were blind-tested.

METAglut1 was 80% sensitive and over 99% specific for Glut1DS diagnosis. A concordance analysis showed a significant agreement between the test and glycorrhachia testing. The positive predictive value of the test in the prospective cohort was slightly higher than that of traditional testing. The test successfully identified patients with Glut1DS with SCL2A1 mosaicism and other variants for which the significances are still unknown.

The study was the largest reported for Glut1DS and reinforce the clinical relevance of the METAglut1 test. However, the researchers were not able to formally establish the diagnostic time gained with the test because most investigators opted to run the test alongside traditional diagnostics simultaneously during clinic visits for practical reasons.

“With a typical turnaround of 48 hours, the [METAglut1] test is robust with few retests necessary, thus warranting an easy adoption in routine clinical settings, notably in outpatient clinics. METAglut1 can be proposed as a first-line investigation to test for Glut1DS without the constraints of a spinal tap, fasting, or expertise to interpret metabolic changes related to age,” the authors explained.

Reference

Mochel F, Gras D, Luton M-P, et al. Prospective Multicenter validation of a simple blood test for the diagnosis of Glut1 deficiency syndrome. Neurology. 2023;100:e2360-e2373. doi:10.1212/WNL.0000000000207296