A novel blood test for Glut1 deficiency syndrome (Glut1DS) performs as well as more invasive and expensive testing, which could create opportunities for more widespread and prompter screening of this rare and treatable disease. These are the findings of a study published in the journal Neurology.
The current standard diagnostic workup relies both on lumbar puncture, to measure cerebrospinal fluid (CSF) glucose, and on molecular testing for mutations of the implicated SLC2A1 gene. However, the new blood assay, METAglut1, can detect the Glut1 glycoprotein on the surface of red blood cells. Now approved in the European Union, it leverages readily available flow cytometry technology, and does not require fasting. METAglut1 researchers wished to determine the prospective accuracy of this test, and directly compare it with the standard-of-care tests for Glut1DS.
In 33 health care centers in France, between September 2018 and March 2021, the researchers recruited both a prospective (n=428) cohort of patients with suspected Glut1DS, and a retrospective cohort (n=67) of patients with previously confirmed Glut1DS. All were age 3 months through adulthood; the majority of patients in each cohort were between 2 and 18 years old. Patients in the prospective cohort participated in both the blood test and reference (CSF and genetic analytical) diagnostic testing; the retrospective cohort took the blood test only. In cases of discordant or uncertain results, gold-standard erythrocyte glucose uptake was tested ex vivo as well. Laboratories performing the tests were blind to patients’ reference diagnostic and clinical data; the investigators were blinded to results as well, to eliminate bias in clinical care.
The positive predictive value for the METAglut1 test, among the prospective cohort, was 90% (95% CI, 71-100), exceeding that of the CSF test; the negative predictive value was 97% (95% CI, 95-100%). Overall specificity >99%; overall sensitivity was 80%. This 1-in-5 false-negative rate likely reflected missense mutations of SCL2A1 that would alter Glut1 function at the blood-brain barrier but not in the erythrocyte membrane. Accordingly, the gold-standard functional glucose uptake test also was negative in these patients.
Concordance was high between the blood and CSF tests, for the combined prospective and retrospective cohorts (Cohen kappa coefficient = .78 [95% CI, 0.69–0.87; P <.001]).
Study limitations included lack of reported patient ethnicity data. Also, the inherently small sample size and other study constraints limited head-to-head statistical comparisons of test accuracy and of time required to obtain test results.
Given this demonstrated accuracy, and its ease of adoption, the researchers recommended using the METAglut1 test early in workup for any patients over 3 months old with a history and signs suggestive of Glut1DS. They emphasized that “Glut1DS is an urgent diagnosis for patients, not to miss critical time where early treatments can be initiated to support brain development and function.”
Disclosures: Several study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of the author’s disclosures.
Mochel F, Gras D, Luton MP, et al. Prospective multicenter validation of a simple blood test for the diagnosis of Glut1 deficiency syndrome. Neurology. 2023;100(23):e2360-e2373. doi:10.1212/WNL.0000000000207296