Clinical presentation, EEG studies, and novel mutations in two cases of GLUT1 deficiency syndrome in Japan.

We report the first two Japanese children diagnosed with glucose transporter type 1 (GLUT1) deficiency syndrome. Both boys had been treated under the initial diagnosis of epilepsy and were reinvestigated for previously unexplainable hypoglycorrhachia. Myoclonic seizures developed at 4 months of age in Patient #1 (7 years old), and at 2 months of age in Patient #2 (11 years old), followed by cerebellar ataxia, spastic diplegia, and mental retardation. Both patients had hypoglycorrhachia, and the symptoms were more severe in the latter. CSF and serum glucose levels determined simultaneously showed a CSF/serum glucose ratio of below 0.4 in both patients. In mildly affected Patient #1, the postprandial waking EEG showed improvement in the background activity, as compared to that recorded after overnight fasting, while no significant changes were observed in severely affected Patient #2. In both patients, the functional GLUT1 defect was confirmed by 3-O-methyl-D-glucose uptake into erythrocytes. Molecular analyses identified heterozygous novel mutations in both patients, within exons 6 and 2 of the GLUT1 gene, respectively. The ketogenic diet was refused in Patient #1, but started in Patient #2 with significant clinical benefit. Fasting CSF analysis and pre-/postprandial EEG changes in children with epileptic seizures and unexplainable neurological deterioration help in diagnosing this potentially treatable disorder.