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Screening of SLC2A1 in a large cohort of patients suspected for Glut1 deficiency syndrome: identification of novel variants and associated phenotypes


Glucose transporter type 1 deficiency syndrome (Glut1 DS) is a rare neurological disorder caused by impaired glucose delivery to the brain. The clinical spectrum of Glut1 DS mainly includes epilepsy, paroxysmal dyskinesia (PD), developmental delay and microcephaly. Glut1 DS diagnosis is based on the identification of hypoglycorrhachia and pathogenic mutations of the SLC2A1 gene. Here, we report the molecular screening of SLC2A1 in 354 patients clinically suspected for Glut1 DS. From this cohort, we selected 245 patients for whom comprehensive clinical and laboratory data were available. Among them, we identified 19 patients carrying nucleotide variants of pathological significance, 5 of which were novel. The symptoms of onset, which varied from neonatal to adult age, included epilepsy, PD or non-epileptic paroxysmal manifestations. The comparison of the clinical features between the 19 SLC2A1 mutated and the 226 non-mutated patients revealed that the onset of epilepsy within the first year of life (when associated with developmental delay or other neurological manifestations), the association of epilepsy with PD and acquired microcephaly are more common in mutated subjects. Taken together, these data confirm the variability of expression of the phenotypes associated with mutation of SLC2A1 and provide useful clinical tools for the early identification of subjects highly suspected for the disease.

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The authors are deeply grateful to: Drs Francesca Darra (Child Neuropsychiatry, University of Verona), Stefania Bergamoni (Azienda Ospedaliera Ospedale Niguarda Ca’ Granda, Milano), Monica Lodi (Centro Regionale per l’Epilessia, Asst Fatebenefratelli Sacco, Milano) and Carmen Bonino (Torino) for referring patients and to Dr. Sara Matricardi (Department of Neuropsychiatry, Children’s Hospital “G. Salesi”, Ospedali Riuniti, Ancona) for her help with statistical analysis.


The present work was supported by the Bando Cariplo 2010 per la ricerca Biomedica no. 2010.0759, the Italian Ministry of Health Ricerca Finalizzata Giovani Ricercatori 2010 (Project GR-2010-2304834 to JCD) and Ricerca Finalizzata Giovani Ricercatori 2016 (Project GR-2016-02363337 to JCD), and Grants from the Pierfranco and Luisa Mariani Foundation (to TG).

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Authors and Affiliations



Genetic screening and analysis, writing of the manuscript (BC, AV, CG); selection of patients, collection and analysis of clinical data (FR, EF, SC, RS, GT, BS, NN, TG); selection of patients, collection of clinical and EEG data (LC, FV, SF); clinical and genetic data analysis, writing of the manuscript (BC, FR, JCD); clinical and genetic data analysis, writing of the manuscript, coordination of the selection of patients, final supervision of the manuscript and submission (CG, TG).

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Correspondence to Jacopo C. DiFrancesco or Tiziana Granata.

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On behalf of all authors, the corresponding author states that there is no conflict of interest.

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Castellotti, B., Ragona, F., Freri, E. et al. Screening of SLC2A1 in a large cohort of patients suspected for Glut1 deficiency syndrome: identification of novel variants and associated phenotypes. J Neurol 266, 1439–1448 (2019).

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  • Glut1 deficiency
  • SLC2A1
  • Hypoglycorrhachia
  • Epilepsy
  • Movement disorder
  • Intellectual disability
  • Developmental delay