title: Glucose transporter type 1 deficiency syndrome with carbohydrate-responsive symptoms but without epilepsy.
abstract: Glucose transporter type 1 deficiency syndrome (GLUT1-DS) is caused by a defect in glucose transport across the blood-brain barrier. The main symptoms are epilepsy, developmental delay, movement disorders, and deceleration of head circumference. A ketogenic diet has been shown to be effective in controlling epilepsy in GLUT1-DS. We report a female child (3 y 4 mo) who presented with delayed psychomotor development and frequent episodes of staggering, impaired vigilance, and vomiting that resolved promptly after food intake. Electroencephalography was normal. The cerebrospinal fluid-blood glucose ratio was 0.42 (normal ≥ 0.45). GLUT1-DS was confirmed by molecular genetic testing, which showed a novel de novo heterozygous mutation in the SLC2A1 gene (c.497_499delTCG, p.VAL166del). Before starting a ketogenic diet, the child's cognitive development was tested using the Snijders-Oomen Non-Verbal Intelligence Test, which revealed a heterogeneous intelligence profile with deficits in her visuomotor skills and spatial awareness. Her motor development was delayed. Three months after introducing a ketogenic diet, she showed marked improvement in speech and motor development, as tested by the Movement Assessment Battery for Children (manual dexterity 16th centile, ball skills 1st centile, static and dynamic balance 5th centile). This case demonstrates that GLUT1-DS should be investigated in individuals with unexplained developmental delay. Epilepsy is not a mandatory symptom. The ketogenic diet is also beneficial for non-epileptic symptoms in GLUT1-DS.
authors.affiliation: Department of General Paediatrics, University Children's Hospital, Düsseldorf, Germany. Anne.Koy@med.uni-duesseldorf.de
authors.forename: Anne
authors.initials: A
authors.lastname: Koy
authors.forename: Birgit
authors.initials: B
authors.lastname: Assmann
authors.forename: Joerg
authors.initials: J
authors.lastname: Klepper
authors.forename: Ertan
authors.initials: E
authors.lastname: Mayatepek
mesh_terms: D001786:Blood Glucose / Q000235:genetics; D002239:Carbohydrate Metabolism, Inborn Errors / Q000134:cerebrospinal fluid / Q000503:physiopathology* / Q000628:therapy; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics; D055423:Diet, Ketogenic / Q000706:statistics & numerical data*; D004827:Epilepsy / Q000235:genetics; D005260:Female; D044882:Glucose Metabolism Disorders / Q000235:genetics / Q000503:physiopathology; D051272:Glucose Transporter Type 1 / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D009004:Monosaccharide Transport Proteins / Q000134:cerebrospinal fluid / Q000172:deficiency; D009069:Movement Disorders / Q000175:diagnosis / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009483:Neuropsychological Tests; D013577:Syndrome
chemical_list: D001786:Blood Glucose; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; C495677:SLC2A1 protein, human