title: Sporadic and familial glut1ds Italian patients: A wide clinical variability.
abstract: OBJECTIVE
  GLUT1 deficiency syndrome is a treatable neurological disorder characterized by developmental delay, movement disorders and epilepsy. It is caused by mutations in the SLC2A1 gene inherited as an autosomal dominant trait with complete penetrance, even if most detected SCL2A1 mutations are de novo. Our aim is to present a wide series of Italian patients to highlight the differences among subjects with de novo mutations and those with familial transmission.
  
  
  METHODS
  We present clinical and genetic features in a series of 22 GLUT1DS Italian patients. Our patients were classified in two different groups: familial cases including GLUT1DS patients with genetically confirmed affected relatives and sporadic cases with detection of SLC2A1 de novo mutation.
  
  
  RESULTS
  We found remarkable differences in the severity of the clinical picture regarding the type of genetic inheritance (sporadic versus familial): sporadic patients were characterized by an earlier epilepsy-onset and higher degree of intellectual disability. No significant differences were found in terms of type of movement disorder, whilst Paroxysmal Exertion-induced Dyskinesia (PED) is confirmed to be the most characteristic movement disorder type in GLUT1DS. In familial cases the clinical manifestation of the disease was particularly variable and heterogeneous, also including asymptomatic patients or those with minimal-symptoms.
  
  
  CONCLUSIONS
  The finding of a "mild" phenotype in familial GLUT1DS gives rise to several questions: the real incidence of the disease, treatment option with ketogenic diet in adult patients and genetic counseling.
authors.affiliation: Brain and Behaviour Department, University of Pavia, Pavia, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: De Giorgis
authors.affiliation: Child and Adolescence Neuropsychiatry Unit, "G. Salvini" Hospital, Rho, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Teutonico
authors.affiliation: "C. Mondino" National Neurological Institute, Pavia, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Cereda
authors.affiliation: Brain and Behaviour Department, University of Pavia, Pavia, Italy; Department of Child Neurology and Psychiatry, "C. Mondino" National Neurological Institute, Pavia, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Balottin
authors.affiliation: "C. Mondino" National Neurological Institute, Pavia, Italy.
authors.forename: Marika
authors.initials: M
authors.lastname: Bianchi
authors.affiliation: Pediatric Neuropsychiatric Division, Spedali Civili, Brescia, Italy.
authors.forename: Lucio
authors.initials: L
authors.lastname: Giordano
authors.affiliation: Brain and Behaviour Department, University of Pavia, Pavia, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Olivotto
authors.affiliation: Department of Child Neurology, Fondazione IRCCS Istituto Neurologico "C. Besta", Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ragona
authors.affiliation: Human Nutrition and Eating Disorders Research Centre, University of Pavia, Pavia, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Tagliabue
authors.affiliation: Department of Child Neurology, Fondazione IRCCS Istituto Neurologico "C. Besta", Milan, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Zorzi
authors.affiliation: Department of Child Neurology, Fondazione IRCCS Istituto Neurologico "C. Besta", Milan, Italy.
authors.forename: Nardo
authors.initials: N
authors.lastname: Nardocci
authors.affiliation: Brain and Behaviour Department, University of Pavia, Pavia, Italy; Department of Child Neurology and Psychiatry, "C. Mondino" National Neurological Institute, Pavia, Italy. Electronic address: pveggiot@unipv.it.
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Veggiotti
mesh_terms: D000293:Adolescent; D000328:Adult; D002239:Carbohydrate Metabolism, Inborn Errors / Q000145:classification* / Q000150:complications* / Q000178:diet therapy / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000178:diet therapy / Q000209:etiology / Q000235:genetics; D055423:Diet, Ketogenic / Q000379:methods; D004569:Electroencephalography; D004827:Epilepsy / Q000178:diet therapy / Q000209:etiology* / Q000235:genetics; D005192:Family Health; D005260:Female; D056726:Genetic Association Studies; D051272:Glucose Transporter Type 1 / Q000235:genetics*; D006801:Humans; D007558:Italy; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins / Q000145:classification / Q000172:deficiency* / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D055815:Young Adult
chemical_list: D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins
keywords: Cognitive impairment; Epilepsy; GLUT1 deficiency syndrome; Ketogenic diet; Paroxysmal exercise-induced dyskinesia; SLC2A1 gene