title: T295M-associated Glut1 deficiency syndrome with normal erythrocyte 3-OMG uptake.
abstract: OBJECTIVE
  Glucose transporter type 1 (Glut1) is expressed in vascular endothelial cells comprising blood-brain barrier. Glut1 deficiency syndrome is characterized by low cerebrospinal fluid (CSF) concentration of glucose with normoglycemia, infantile seizure, acquired microcephaly, developmental delay and ataxia. As Glut1 is also expressed in erythrocytes, the diagnosis is confirmed by a decreased uptake of 3-O-methylglucose (3-OMG) into erythrocytes. However, patients with T295M mutation in the Glut1 gene show normal 3-OMG uptake. An in vitro study has proved that the T295M affects efflux rather than influx of glucose, explaining the discrepancy. However, the normal 3-OMG uptake in erythrocytes still indicates a possibility that the phenotype associated with this particular mutation may be milder. We compared the phenotype of three T295M-associated patients with that of other Glut1-deficient patients.
  
  
  METHODS
  Two patients are from our clinic and one is a patient reported elsewhere. The phenotype and biochemical data of patients with mutations other than T295M were obtained from a review and our previous report.
  
  
  RESULTS
  Despite the normal 3-OMG uptake into erythrocytes, all patients with T295M showed decreased glucose levels in CSF (33, 31 and 38mg/dl, respectively). The levels were comparable to those in patients with mutations other than T295M (31±4.3mg/dl (n=45)). All patients had convulsion, ataxia, speech delay, microcephaly and spasticity.
  
  
  CONCLUSIONS
  Despite the normal 3-OMG uptake in erythrocytes, phenotype of T295M-associated Glut1 deficiency was not significantly different from that of patients with a deficient 3-OMG uptake, indicating that T295M affects the glucose transport at the blood-brain barrier as much as other mutations.
authors.affiliation: Department of Pediatrics, Shiga Medical Center for Children, 5-7-30 Moriyama, Shiga, Japan. tatsu-fu@mx.biwa.ne.jp
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Fujii
authors.forename: Masafumi
authors.initials: M
authors.lastname: Morimoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yoshioka
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Ho
authors.forename: Peggy P Y
authors.initials: PP
authors.lastname: Law
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.forename: Darryl C
authors.initials: DC
authors.lastname: De Vivo
mesh_terms: D019325:3-O-Methylglucose / Q000097:blood*; D000293:Adolescent; D002648:Child; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D051272:Glucose Transporter Type 1 / Q000172:deficiency* / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D013577:Syndrome
chemical_list: D051272:Glucose Transporter Type 1; D019325:3-O-Methylglucose