title: Seizures, ataxia, developmental delay and the general paediatrician: glucose transporter 1 deficiency syndrome.
abstract: OBJECTIVE
  Glucose transporter 1 deficiency syndrome (GLUT1-DS) is an important condition for the general paediatrician's differential armamentarium. We describe a case series of eight patients in order to raise awareness of this treatable neurometabolic condition. The diagnosis of GLUT1-DS is suggested by a decreased absolute cerebrospinal fluid (CSF) glucose value (<2.2 mmol/L) or lowered CSF: plasma glucose ratio (<0.4).
  
  
  METHODS
  This is a review of eight Queensland patients with GLUT1-DS. The clinical presentation, clinical course, laboratory investigations and treatment outcomes are discussed.
  
  
  RESULTS
  The clinical features noted in our patient cohort include combinations of ataxia, developmental delay and a severe seizure disorder that is refractory to anticonvulsant medications. Seizures are the most common clinical manifestation and may be exacerbated by phenobarbitone. The paired CSF: plasma glucose results ranged from 0.2 to 0.39 (normal <0.6) with an average of 0.33. 3-O-Methyl-D-Glucose uptake and GLUT1 Genotyping analysis have been performed on five patients thus far. Rapid and impressive seizure control was observed in 100% of our patients once the ketogenic diet was instituted, with half of the cohort being able to wean completely from anticonvulsants.
  
  
  CONCLUSIONS
  Children presenting with a clinical phenotype consisting of a refractory seizure disorder, ataxia and developmental delay should prompt the consideration of Glucose transporter 1 deficiency syndrome. While the diagnostic test of lumbar puncture is an invasive manoeuvre, the diagnosis provides a viable treatment option, the ketogenic diet. GLUT1-DS displays clinical heterogeneity, but the value of early diagnosis and treatment is demonstrated by our patient cohort.
authors.affiliation: Department of Metabolic Medicine, The Royal Children's Hospital, Brisbane, Queensland, Australia. david_coman@health.qld.gov.au
authors.forename: David J
authors.initials: DJ
authors.lastname: Coman
authors.forename: K G
authors.initials: KG
authors.lastname: Sinclair
authors.forename: C J
authors.initials: CJ
authors.lastname: Burke
authors.forename: D B
authors.initials: DB
authors.lastname: Appleton
authors.forename: J T
authors.initials: JT
authors.lastname: Pelekanos
authors.forename: C M
authors.initials: CM
authors.lastname: O'Neil
authors.forename: G B
authors.initials: GB
authors.lastname: Wallace
authors.forename: F G
authors.initials: FG
authors.lastname: Bowling
authors.forename: D
authors.initials: D
authors.lastname: Wang
authors.forename: D C
authors.initials: DC
authors.lastname: De Vivo
authors.forename: J J
authors.initials: JJ
authors.lastname: McGill
mesh_terms: D019325:3-O-Methylglucose / Q000493:pharmacokinetics; D000927:Anticonvulsants / Q000627:therapeutic use; D001259:Ataxia / Q000209:etiology*; D020739:Brain Diseases, Metabolic, Inborn / Q000175:diagnosis / Q000178:diet therapy* / Q000209:etiology*; D002239:Carbohydrate Metabolism, Inborn Errors / Q000178:diet therapy / Q000209:etiology; D002648:Child; D002658:Developmental Disabilities / Q000209:etiology*; D004035:Diet Therapy; D005260:Female; D051272:Glucose Transporter Type 1 / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D007223:Infant; D008159:Lumbar Vertebrae; D008297:Male; D012640:Seizures / Q000188:drug therapy / Q000209:etiology*; D013129:Spinal Puncture; D013577:Syndrome; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D051272:Glucose Transporter Type 1; D019325:3-O-Methylglucose