A blood test can detect glucose transporter type 1 (GLUT1) deficiency syndrome accurately and rapidly, according to a brief communication published in the July issue of Annals of Neurology. The new test has a diagnostic rate comparable to that of CSF glucose and may be more cost-effective than the combination of lumbar puncture and genetic testing, according to the researchers.
To confirm the diagnosis in a patient whose phenotype suggests GLUT1 deficiency syndrome, neurologists traditionally measure CSF glucose concentration and perform SLC2A1 molecular analysis. Lumbar puncture requires fasting and may entail complications, however, and analysis of the coding regions of SLC2A1 can be tedious and may fail to identify variants.
Analysis of Red Blood Cells
Domitille Gras, MD, a neurologist at Robert-Debré University Hospital in Paris, and colleagues tested a novel diagnostic method based on flow cytometry analysis of red blood cells. For their proof-of-concept study, the researchers enrolled 30 patients (13 females) between ages 2 and 50 with GLUT1 deficiency syndrome. They also enrolled 18 patients (six females) with paroxysmal movement disorders attributed to genetic defects other than in SLC2A1. Finally, the investigators examined 346 healthy controls.
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.
Age Did Not Affect Test Results
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.
Gras D, Cousin C, Kappeler C, et al. A simple blood test expedites the diagnosis of glucose transporter type 1 deficiency syndrome. Ann Neurol. 2017;82(1):133-138.