Imaging the metabolic footprint of Glut1 deficiency on the brain.

Cerebral 18F-fluorodeoxyglucose positron emission tomography in 14 patients with microcephaly, developmental delay, seizures, and mutations of the glucose transporter Glut1 (Glut1 deficiency syndrome) showed distinct abnormalities. Within a global context of diminished cortical uptake, more severe hypometabolism was found in the mesial temporal regions and thalami, accentuating a relative signal increase in the basal ganglia. In contrast, the structure of the brain appeared preserved in patients additionally investigated by magnetic resonance imaging. This metabolic footprint was relatively constant in all patients regardless of age, seizure history, or therapies and therefore constitutes a radiological signature of the disease. The full expression of the signature in the youngest patient (aged 19 months) indicates that the state of haploinsufficiency caused by Glut1 mutation leaves a permanent footprint on the nervous system from its earlier postnatal stages of development. The potential benefit of prompt diagnosis, aided by 18F-fluorodeoxyglucose positron emission tomography, and early initiation of available therapies is underscored by our results.