Glut1 deficiency syndrome and erythrocyte glucose uptake assay

Objective: The Glut1 deficiency syndrome (Glut1 DS) phenotype has expanded dramatically since first described in 1991. Hypoglycorrhachia and decreased erythrocyte 3‐OMG uptake are confirmatory laboratory biomarkers. The objective is to expand previous observations regarding the diagnostic value of the uptake assay. Methods: One hundred and nine suspected cases of Glut‐1 DS were studied. All cases had a consistent clinical picture and hypoglycorrhachia. The uptake assay was decreased in 74 cases (group 1) and normal in 35 cases (group 2). We identified disease‐causing mutations in 70 group 1 patients (95%) and one group 2 patient (3%). Results: The cut‐off for an abnormally low uptake value was increased from 60% to 74% with a corresponding sensitivity of 99% and specificity of 100%. The correlation between the uptake values for the time‐curve and the kinetic concentration curve were strongly positive (R2 = 0.85). Significant group differences were found in CSF glucose and lactate values, tone abnormalities, and degree of microcephaly. Group 2 patients were less affected in all domains. We also noted a significant correlation between the mean erythrocyte 3‐OMG uptake and clinical severity (R2 = 0.94). Interpretation: These findings validate the erythrocyte glucose uptake assay as a confirmatory functional test for Glut1 DS and as a surrogate marker for GLUT1 haploinsufficiency. ANN NEUROL 2011;70:996–1005