title: Glut1 deficiency syndrome and erythrocyte glucose uptake assay.
abstract: OBJECTIVE
  The Glut1 deficiency syndrome (Glut1 DS) phenotype has expanded dramatically since first described in 1991. Hypoglycorrhachia and decreased erythrocyte 3-OMG uptake are confirmatory laboratory biomarkers. The objective is to expand previous observations regarding the diagnostic value of the uptake assay.
  
  
  METHODS
  One hundred and nine suspected cases of Glut-1 DS were studied. All cases had a consistent clinical picture and hypoglycorrhachia. The uptake assay was decreased in 74 cases (group 1) and normal in 35 cases (group 2). We identified disease-causing mutations in 70 group 1 patients (95%) and one group 2 patient (3%).
  
  
  RESULTS
  The cut-off for an abnormally low uptake value was increased from 60% to 74% with a corresponding sensitivity of 99% and specificity of 100%. The correlation between the uptake values for the time-curve and the kinetic concentration curve were strongly positive (R(2) = 0.85). Significant group differences were found in CSF glucose and lactate values, tone abnormalities, and degree of microcephaly. Group 2 patients were less affected in all domains. We also noted a significant correlation between the mean erythrocyte 3-OMG uptake and clinical severity (R(2) = 0.94).
  
  
  CONCLUSIONS
  These findings validate the erythrocyte glucose uptake assay as a confirmatory functional test for Glut1 DS and as a surrogate marker for GLUT1 haploinsufficiency.
authors.affiliation: Colleen Giblin Laboratories for Pediatric Neurology Research, Department of Neurology, Columbia University, New York, NY 10032, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.forename: Kristin
authors.initials: K
authors.lastname: Engelstad
authors.forename: Leslie
authors.initials: L
authors.lastname: Bagay
authors.forename: Ying
authors.initials: Y
authors.lastname: Wei
authors.forename: Michael
authors.initials: M
authors.lastname: Rotstein
authors.forename: Vimla
authors.initials: V
authors.lastname: Aggarwal
authors.forename: Brynn
authors.initials: B
authors.lastname: Levy
authors.forename: Lijiang
authors.initials: L
authors.lastname: Ma
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Chung
authors.forename: Darryl C
authors.initials: DC
authors.lastname: De Vivo
mesh_terms: D001786:Blood Glucose / Q000378:metabolism*; D002675:Child, Preschool; D004912:Erythrocytes / Q000378:metabolism*; D005192:Family Health; D005260:Female; D051272:Glucose Transporter Type 1 / Q000172:deficiency* / Q000235:genetics; D006151:Guanosine / Q000031:analogs & derivatives / Q000097:blood / Q000134:cerebrospinal fluid; D006801:Humans; D007223:Infant; D008297:Male; D008659:Metabolic Diseases / Q000097:blood* / Q000134:cerebrospinal fluid / Q000150:complications / Q000235:genetics; D009154:Mutation / Q000235:genetics; D012372:ROC Curve; D012640:Seizures / Q000209:etiology; D012720:Severity of Illness Index; D013223:Statistics as Topic
chemical_list: D001786:Blood Glucose; D051272:Glucose Transporter Type 1; C495677:SLC2A1 protein, human; C037626:3'-O-methylguanosine; D006151:Guanosine