title: Absence epilepsies with widely variable onset are a key feature of familial GLUT1 deficiency.
abstract: BACKGROUND
  Familial glucose transporter type 1 (GLUT1) deficiency due to autosomal dominant inheritance of SLC2A1 mutations is associated with paroxysmal exertional dyskinesia; epilepsy and intellectual disability occur in some family members. We recently demonstrated that GLUT1 deficiency occurs in over 10% of patients with early-onset absence epilepsy.
  
  
  METHODS
  This family study analyses the phenotypes in 2 kindreds segregating SLC2A1 mutations identified through probands with early-onset absence epilepsy. One comprised 9 individuals with mutations over 3 generations; the other had 6 individuals over 2 generations.
  
  
  RESULTS
  Of 15 subjects with SLC2A1 mutations, epilepsy occurred in 12. Absence seizures were the most prevalent seizure type (10/12), with onset from 3 to 34 years of age. Epilepsy phenotypes varied widely, including idiopathic generalized epilepsies (IGE) with absence (8/12), myoclonic-astatic epilepsy (2/12), and focal epilepsy (2/12). Paroxysmal exertional dyskinesia occurred in 7, and was subtle and universally undiagnosed prior to molecular diagnosis. There were 2 unaffected mutation carriers.
  
  
  CONCLUSIONS
  GLUT1 deficiency is an important monogenic cause of absence epilepsies with onset from early childhood to adult life. Individual cases may be phenotypically indistinguishable from common forms of IGE. Although subtle paroxysmal exertional dyskinesia is a helpful diagnostic clue, it is far from universal. The phenotypic spectrum of GLUT1 deficiency is considerably greater than previously recognized. Diagnosis of GLUT1 deficiency has important treatment and genetic counseling implications.
authors.affiliation: Epilepsy Research Centre, Neuroscience Building, Department of Medicine, The University of Melbourne, Austin Health, Melbourne, Australia.
authors.forename: S A
authors.initials: SA
authors.lastname: Mullen
authors.forename: A
authors.initials: A
authors.lastname: Suls
authors.forename: P
authors.initials: P
authors.lastname: De Jonghe
authors.forename: S F
authors.initials: SF
authors.lastname: Berkovic
authors.forename: I E
authors.initials: IE
authors.lastname: Scheffer
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D002819:Chorea / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000235:genetics; D004832:Epilepsy, Absence / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000235:genetics*; D005190:Family; D005947:Glucose / Q000134:cerebrospinal fluid; D051272:Glucose Transporter Type 1 / Q000172:deficiency* / Q000235:genetics*; D006801:Humans; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D055815:Young Adult
chemical_list: D051272:Glucose Transporter Type 1; C495677:SLC2A1 protein, human; D005947:Glucose