Seizures, ataxia, developmental delay and the general paediatrician: glucose transporter 1 deficiency syndrome.
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.
Coman
David J
DJ
Department of Metabolic Medicine, The Royal Children's Hospital, Brisbane, Queensland, Australia. david_coman@health.qld.gov.au
Sinclair
K G
KG
Burke
C J
CJ
Appleton
D B
DB
Pelekanos
J T
JT
O'Neil
C M
CM
Wallace
G B
GB
Bowling
F G
FG
Wang
D
D
De Vivo
D C
DC
McGill
J J
JJ
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
D000927:Anticonvulsants; D051272:Glucose Transporter Type 1; D019325:3-O-Methylglucose