Gras D, Cousin C, Kappeler C, Fung CW, Auvin S, Essid N, Chung BH, Da Costa L, Hainque E, Luton MP, Petit V, Vuillaumier-Barrot S, Boespflug-Tanguy O, Roze E, Mochel F. A simple blood test expedites the diagnosis of glucose transporter type 1 deficiency syndrome. Ann Neurol. 2017 Jul;82(1):133-138.
Glucose transporter type 1 (GLUT1) deficiency syndrome (GLUT1-DS) leads to a wide range of neurological symptoms. Ketogenic diets are very efficient to control epilepsy and movement disorders. We tested a novel simple and rapid blood test in 30 patients with GLUT1-DS with predominant movement disorders, 18 patients with movement disorders attributed to other genetic defects, and 346 healthy controls. We detected significantly reduced GLUT1 expression only on red blood cells from patients with GLUT1-DS (23 patients; 78%), including patients with inconclusive genetic analysis. This test opens perspectives for the screening of GLUT1-DS in children and adults with cognitive impairment, movement disorder, or epilepsy.
For all participants, Dr. Gras and colleagues measured CSF glucose concentration, performed SLC2A1 molecular analysis, and used flow cytometry to analyze GLUT1 surface expression on circulating red blood cells. To perform the latter method, researchers who were blinded to patients’ disease condition collected at least 0.5 mL of nonfasted venous blood from each participant. Results were available within 24 hours.
GLUT1 expression on red blood cells varied by 15% among healthy controls. The blood test identified 23 (78%) of the patients with GLUT1 deficiency syndrome who had a decrease in GLUT1 expression of at least 20%. Dr. Gras and colleagues saw no overlap between the test results of patients and those of controls. The new test detected three patients with GLUT1 deficiency syndrome who had a CSF glucose concentration greater than 2.2 mM, which is the most commonly used cutoff. Two patients with a presentation suggestive of GLUT1 deficiency syndrome and low CSF glucose and lactate, but no SLC2A1 mutation, had an abnormal blood test.
The blood test detected GLUT1 deficiency syndrome regardless of the patient’s age and disease severity. Patients not detected by the test may have mutations that mildly affect glucose uptake, but not GLUT1 expression, or may have a GLUT1 deficiency restricted to the brain. Most patients were analyzed at least twice, and blood test results were consistent for each patient.
Measuring GLUT1 at the surface of red blood cells could avoid diagnostic delays that currently are considerable, said Dr. Gras and colleagues. “Although more studies are required to establish the diagnostic gain of the red blood cell test on a larger cohort, such a simple diagnostic test, readily available in clinical practice, ought to greatly enlarge the screening of GLUT1 deficiency syndrome in any patient, child, or adult presenting with cognitive impairment, epilepsy, ataxia and/or dystonia, or paroxysmal movement disorder,” they concluded.