H.Y. and D.W. contributed equally to this work.
Glut1 deficiency syndrome and erythrocyte glucose uptake assay
Article first published online: 21 DEC 2011
Copyright © 2011 American Neurological Association
Annals of Neurology
Volume 70, Issue 6, pages 996–1005, December 2011
How to Cite
Yang, H., Wang, D., Engelstad, K., Bagay, L., Wei, Y., Rotstein, M., Aggarwal, V., Levy, B., Ma, L., Chung, W. K. and De Vivo, D. C. (2011), Glut1 deficiency syndrome and erythrocyte glucose uptake assay. Ann Neurol., 70: 996–1005. doi: 10.1002/ana.22640
- Issue published online: 21 DEC 2011
- Article first published online: 21 DEC 2011
- Accepted manuscript online: 10 OCT 2011 10:46AM EST
- Manuscript Accepted: 23 SEP 2011
- Manuscript Revised: 12 AUG 2011
- Manuscript Received: 12 JAN 2011
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.
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%).
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).
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