Abstracts

Rationale: Glucose transporter type 1 (GLUT1) is a primary glucose transporter at the blood-brain barrier. GLUT1 deficiency syndrome (OMIM#606777) is a disorder of brain energy metabolism caused by impaired GLUT1-mediated glucose transport into the brain. This syndrome clinically leads to epilepsy, motor disorder (ataxia), mental impairment and is particularly important in the differential diagnosis of early-onset infantile epilepsy because it could be treatable with ketogenic diet. Although neuroimaging has typically been considered uninformative in this syndrome, there are some reports indicating its white matter abnormalities including delayed myelination. We attempted to determine whether diffusion tensor imaging (DTI) could detect the white matter abnormalities in a patient with GLUT1 deficiency syndrome who has showed delayed myelination by the conventional MRI studies. Methods: We studied 3-year-old girl who had a first seizure at 2 months of age and was diagnosed GLUT1 deficiency syndrome at 3 years of age based on her clinical features, a low glucose concentration in the cerebrospinal fluid in the setting of normoglycemia and reduced glucose uptake into erythrocytes. MRI was performed at 12 months of age and delayed myelination was revealed on T2-weighted images. DTI study was performed at 3 years of age. Fractional anisotropy (FA) map was created from the DTI. Image analysis was carried out using statistical parametric mapping (SPM5) software. FA images were normalized to a standard space and smoothed with a 6mm FWHF isotropic Gausian kernel. We compared the smoothed FA map of the patient with those of 10 normal controls (mean age 3-years 4-months). The threshold for the statistic map was set at p=0.005 and extent threshold at 50 voxels. Results: At 3-years 4-months of age, T2-weighted images showed completed myelination except small high signal intensity areas in the left parietal subcortical white matter. Analysis with FA map revealed decreased FA values in the bilateral posterior limbs of internal capsules, deep white matter around lateral cerebral ventricles and genu of corpus callosum. These lesions could not be noted on the conventional MRI. Conclusions: Analysis with FA map pointed out the white matter abnormalities that conventional MRI failed to detect in a patient with GLUT1 deficiency syndrome. This finding suggests that failure of brain energy metabolism in GLUT1 deficiency syndrome may cause microstructural abnormalities or delayed myelination of white matter that conventional MRI dose not reveal.