Defective Glucose Transport across the Blood-Brain Barrier as a Cause of Persistent Hypoglycorrhachia, Seizures, and Developmental Delay

Open Access
Publisher Website
Google Scholar
Abstract
GLUCOSE (D-glucose) is an essential fuel for the brain and many other tissues. Five glucose-transporter proteins facilitate the diffusion of glucose across lipophilic plasma membranes.1 2 3 This process is saturable and stereospecific, but it is not concentrative, energy dependent, or influenced by sodium. In humans, the erythrocyte glucose transporter (type 1 glucose transporter) has been studied most extensively. It accounts for 2 to 5 percent of the erythrocyte-membrane protein and seems to be identical in molecular weight and antigenic properties to the glucose transporters in the endothelial cells of brain capillaries.4 5 6 7 Brain capillaries contain large amounts of messenger RNA for the type 1 glucose transporter,8 , 9 and the density of these transporters in brain capillaries is approximately 10 times greater than in tissues other than erythrocytes.4 , 5 , 10 , 11 The presence of the type 1 glucose transporter in erythrocytes and brain capillaries provides an opportunity to study genetic conditions that may affect the transport of glucose across the blood–brain barrier. The movement of water-soluble molecules across this barrier is limited by the occluding junctions between endothelial cells and by the scarcity of pinocytosis.12 , 13 Dick et al.4 estimated that capillary endothelial cells in the brain transport about 10 times their weight of glucose per minute to support the glucose requirements of the brain.4 , 14 A defect of the glucose-transporter protein of brain capillaries should interfere with cerebral energy metabolism and brain function. We have studied two children with persistent hypoglycorrhachia (low concentrations of glucose in cerebrospinal fluid), seizures, and delayed development who seemed to have a genetic defect involving the type 1 glucose transporter. Both responded dramatically to treatment with a ketogenic diet. We believe that these two children have a primary defect of glucose transport into the brain.