Sporadic and familial glut1ds Italian patients: A wide clinical variability

Seizure. 2015 Jan:24:28-32. doi: 10.1016/j.seizure.2014.11.009. Epub 2014 Nov 26.

Abstract

Purpose: 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.

Conclusion: 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.

Keywords: Cognitive impairment; Epilepsy; GLUT1 deficiency syndrome; Ketogenic diet; Paroxysmal exercise-induced dyskinesia; SLC2A1 gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Carbohydrate Metabolism, Inborn Errors / classification*
  • Carbohydrate Metabolism, Inborn Errors / complications*
  • Carbohydrate Metabolism, Inborn Errors / diet therapy
  • Carbohydrate Metabolism, Inborn Errors / genetics*
  • Child
  • Child, Preschool
  • Developmental Disabilities / diet therapy
  • Developmental Disabilities / etiology
  • Developmental Disabilities / genetics
  • Diet, Ketogenic / methods
  • Electroencephalography
  • Epilepsy / diet therapy
  • Epilepsy / etiology*
  • Epilepsy / genetics
  • Family Health
  • Female
  • Genetic Association Studies
  • Glucose Transporter Type 1 / genetics*
  • Humans
  • Italy
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Monosaccharide Transport Proteins / classification
  • Monosaccharide Transport Proteins / deficiency*
  • Monosaccharide Transport Proteins / genetics
  • Mutation / genetics*
  • Young Adult

Substances

  • Glucose Transporter Type 1
  • Monosaccharide Transport Proteins

Supplementary concepts

  • Glut1 Deficiency Syndrome