Glucose transport protein deficiency: An emerging syndrome with therapeutic implications

The further definition of a novel clinical syndrome manifested by infantile seizures, acquired microcephaly, developmental delay, and persistent hypoglycorrachia resulting from defective glucose transport across the blood-brain barrier. Ten children with glucose transport protein syndrome (GTPS) were evaluated. Thirty-six lumbar punctures were performed, and the CSF metabolites were compared to normal and disease controls. The effects of age on the CSF/blood glucose ratio was determined; 3-0-methyl-D-glucose uptake by freshly-prepared erythrocytes was used as a physiological measure of the glucose transporter protein I integrity. The CSF glucose and lactate values and the CSF/blood glucose ratio were consistently lower in the 10 patients with the glucose transporter defect when compared with the normal subjects and the disease controls. The CSF/blood glucose ratio was slightly lower in infants less than 60 days of age (0.58). The glucose uptake rates in erythrocytes from the patients with the glucose transporter defect were consistently lower when compared with the parents. Defective glucose transport across the blood brain barrier represents the pathogenic basis for a novel clinical syndrome of infancy. This neurological condition can be treated by initiating a ketogenic diet. Ketone bodies provide an alternative fuel source for cerebral metabolism.