Abstract
Impaired glucose transport across the bloodβbrain barrier results in Glutβ1 deficiency syndrome (Glutβ1 DS, OMIM 606777), characterized by infantile seizures, developmental delay, acquired microcephaly, spasticity, ataxia, and hypoglycorrhachia. We studied 16 new Glutβ1 deficiency syndrome patients focusing on clinical and laboratory features, molecular genetics, genotypeβphenotype correlation, and treatment. These patients were classified phenotypically into three groups. The mean cerebrospinal fluid glucose concentration was 33.1 Β± 4.9mg/dl equal to 37% of the simultaneous blood glucose concentration. The mean cerebrospinal fluid lactate concentration was 1.0 Β± 0.3mM, which was less than the normal mean value of 1.63mM. The mean V~max~ for the 3βOβmethylβDβglucose uptake into erythrocytes was 996 fmol/10^6^ red blood cells per second, significantly less (54 Β± 11%; t test, p < 0.05) than the mean control value of 1,847. The mean Km value for the patient group (1.4 Β± 0.5mM) was similar to the control group (1.7 Β± 0.5mM; t test, p > 0.05). We identified 16 rearrangements, including seven missense, one nonsense, one insertion, and seven deletion mutations. Fourteen were novel mutations. There were no obvious correlations between phenotype, genotype, or biochemical measures. The ketogenic diet produced good seizure control. Ann Neurol 2005;57:111β118