Glut-1 deficiency syndrome: clinical, genetic, and therapeutic aspects.
Impaired glucose transport across the blood-brain barrier results in Glut-1 deficiency syndrome (Glut-1 DS, OMIM 606777), characterized by infantile seizures, developmental delay, acquired microcephaly, spasticity, ataxia, and hypoglycorrhachia. We studied 16 new Glut-1 deficiency syndrome patients focusing on clinical and laboratory features, molecular genetics, genotype-phenotype correlation, and treatment. These patients were classified phenotypically into three groups. The mean cerebrospinal fluid glucose concentration was 33.1 +/- 4.9mg/dl equal to 37% of the simultaneous blood glucose concentration. The mean cerebrospinal fluid lactate concentration was 1.0 +/- 0.3mM, which was less than the normal mean value of 1.63mM. The mean V(max) for the 3-O-methyl-D-glucose uptake into erythrocytes was 996 fmol/10(6) red blood cells per second, significantly less (54 +/- 11%; t test, p < 0.05) than the mean control value of 1,847. The mean Km value for the patient group (1.4 +/- 0.5mM) was similar to the control group (1.7 +/- 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.
Wang
Dong
D
Colleen Giblin Laboratories for Pediatric Neurology Research, Department of Neurology, Columbia University, 710 West 168th Street, New York, NY 10032, USA.
Pascual
Juan M
JM
Yang
Hong
H
Engelstad
Kristin
K
Jhung
Sarah
S
Sun
Ruo Peng
RP
De Vivo
Darryl C
DC
D019325:3-O-Methylglucose / Q000097:blood; D000293:Adolescent; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D002239:Carbohydrate Metabolism, Inborn Errors / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods; D004035:Diet Therapy / Q000379:methods; D004569:Electroencephalography / Q000379:methods; D005091:Exons; D005260:Female; D005947:Glucose / Q000134:cerebrospinal fluid; D051272:Glucose Transporter Type 1; D006801:Humans; D007223:Infant; D007661:Ketoses / Q000627:therapeutic use*; D019344:Lactic Acid / Q000134:cerebrospinal fluid; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000172:deficiency* / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic
D001786:Blood Glucose; D051272:Glucose Transporter Type 1; D007661:Ketoses; D009004:Monosaccharide Transport Proteins; C495677:SLC2A1 protein, human; D019325:3-O-Methylglucose; D019344:Lactic Acid; D005947:Glucose