Children with seizures of unknown etiology and developmental delay constitute a significant proportion of the patients presenting to Pediatric Neurology clinics. In a small subset of such children, these symptoms are due to a defect in the glucose transporter protein, GLUT1(DeVivo et al., New England J Med 325:703, 1991). These children are also characterized by persistent hypoglycorrachia, which provided the first evidence of inadequate glucose delivery to the brain. Although the seizures are not responsive to medication, the children can be maintained symptom-free by adherance to a ketogenic diet, which provides an alternative fuel for cerebral metabolism. GLUT1 belongs to a family of proteins responsible for the transport of glucose across cell membranes, and is specifically responsible for the transport of glucose across the blood-brain barrier, and into non-neuronal cells; transport into neurons is mediated by GLUT3. GLUT1 is also highly concentrated in human erythrocytes (RBCs); GLUT3 is in human platelets. To date, the diagnosis of the GLUT1 deficiency depends upon a spinal tap for the determination of CSF glucose and no GLUT3 defects have been investigated. The purpose of this study was to devise a less invasive screen which could test a larger population of children for potential GLUT1 and GLUT3 deficiencies. The screen we describe requires a 10cc blood sample and provides information on the levels and activities of GLUT1 (RBC) and GLUT3 (platelets), and DNA for further analysis(lymphocytes). Following separation of platelets, lymphocytes, and RBCs, glucose transport activity is measured in platelets by 3H-2- deoxyglucose uptake and in RBCs by equilibrium exchange with14 C-glucose; GLUT1 and GLUT3 levels are determined in RBC and platelet membranes respectively by Western blot analysis. We have validated this screen in known positive patients for the ability to detect the GLUT1 defect. Thus this screen offers a simple, non-invasive opportunity to detect patients with glucose transporter defects and provides the rationale for treatment with the ketogenic diet.
