Glut1 deficiency syndrome and erythrocyte glucose uptake assay

Ann Neurol. 2011 Dec;70(6):996-1005. doi: 10.1002/ana.22640.

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).

Interpretation: These findings validate the erythrocyte glucose uptake assay as a confirmatory functional test for Glut1 DS and as a surrogate marker for GLUT1 haploinsufficiency.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Glucose / metabolism*
  • Child, Preschool
  • Erythrocytes / metabolism*
  • Family Health
  • Female
  • Glucose Transporter Type 1 / deficiency*
  • Glucose Transporter Type 1 / genetics
  • Guanosine / analogs & derivatives
  • Guanosine / blood
  • Guanosine / cerebrospinal fluid
  • Humans
  • Infant
  • Male
  • Metabolic Diseases / blood*
  • Metabolic Diseases / cerebrospinal fluid
  • Metabolic Diseases / complications
  • Metabolic Diseases / genetics
  • Mutation / genetics
  • ROC Curve
  • Seizures / etiology
  • Severity of Illness Index
  • Statistics as Topic

Substances

  • Blood Glucose
  • Glucose Transporter Type 1
  • SLC2A1 protein, human
  • 3'-O-methylguanosine
  • Guanosine