Phenotype variability of GLUT1 deficiency syndrome: Description of a case series with novel SLC2A1 gene mutations

Lidia Di Vito, Laura Licchetta, Tommaso Pippucci, Sara Baldassari, Carlotta Stipa, Barbara Mostacci, Lara Alvisi, Paolo Tinuper, Francesca Bisulli

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Glucose transporter type 1 (GLUT1) deficiency due to SLC2A1 mutations causes a wide spectrum of neurologic disorders ranging from severe encephalopathy with developmental delay, epilepsy, ataxia, and acquired microcephaly to atypical less severe variants. Early diagnosis is crucial for prompt initiation of a ketogenic diet. Recognizing GLUT1 deficiency syndrome (GLUT1DS) may be challenging and results in delayed diagnosis. Here we describe the clinical and molecular findings of patients with SLC2A1 mutations referred to our adult Epilepsy Center. Patients with a clinical history suggestive of GLUT1DS were screened for SLC2A1 mutations. Blood samples were collected from probands and first-degree relatives. A lumbar puncture was performed in two patients in fasting state, and cerebrospinal fluid and blood glucose measurement were undertaken at the same time. Since 2010, 19 GLUT1DS probands have been screened for SLC2A1 mutations. We identified four different SLC2A1 mutations in three sporadic cases and one family. Three mutations (c.130_135delTACAAC, c.342_343insA, and c.845A > G) were novel, whereas one was previously reported in the literature associated with a different phenotype (c.497_499delTCG). Here we describe a small case series of patients with sporadic and familial GLUT1DS presenting with a broad phenotypic heterogeneity which is likely to be responsible for the considerable delay in diagnosis.

Original languageEnglish
Pages (from-to)169-173
Number of pages5
JournalEpilepsy and Behavior
Volume79
DOIs
Publication statusPublished - Feb 1 2018

Fingerprint

Phenotype
Mutation
Genes
Epilepsy
Glucose Transporter Type 1
Ketogenic Diet
Microcephaly
Spinal Puncture
Delayed Diagnosis
Brain Diseases
Ataxia
Nervous System Diseases
Cerebrospinal Fluid
Blood Glucose
Glut1 Deficiency Syndrome
Early Diagnosis
Fasting

Keywords

  • Epilepsy
  • Glucose transporter type I deficiency syndrome
  • Nonepileptic paroxysmal phenomena
  • SLC2A1 mutation

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Behavioral Neuroscience

Cite this

@article{ef5883de121141fc9319200e77c04786,
title = "Phenotype variability of GLUT1 deficiency syndrome: Description of a case series with novel SLC2A1 gene mutations",
abstract = "Glucose transporter type 1 (GLUT1) deficiency due to SLC2A1 mutations causes a wide spectrum of neurologic disorders ranging from severe encephalopathy with developmental delay, epilepsy, ataxia, and acquired microcephaly to atypical less severe variants. Early diagnosis is crucial for prompt initiation of a ketogenic diet. Recognizing GLUT1 deficiency syndrome (GLUT1DS) may be challenging and results in delayed diagnosis. Here we describe the clinical and molecular findings of patients with SLC2A1 mutations referred to our adult Epilepsy Center. Patients with a clinical history suggestive of GLUT1DS were screened for SLC2A1 mutations. Blood samples were collected from probands and first-degree relatives. A lumbar puncture was performed in two patients in fasting state, and cerebrospinal fluid and blood glucose measurement were undertaken at the same time. Since 2010, 19 GLUT1DS probands have been screened for SLC2A1 mutations. We identified four different SLC2A1 mutations in three sporadic cases and one family. Three mutations (c.130_135delTACAAC, c.342_343insA, and c.845A > G) were novel, whereas one was previously reported in the literature associated with a different phenotype (c.497_499delTCG). Here we describe a small case series of patients with sporadic and familial GLUT1DS presenting with a broad phenotypic heterogeneity which is likely to be responsible for the considerable delay in diagnosis.",
keywords = "Epilepsy, Glucose transporter type I deficiency syndrome, Nonepileptic paroxysmal phenomena, SLC2A1 mutation",
author = "{Di Vito}, Lidia and Laura Licchetta and Tommaso Pippucci and Sara Baldassari and Carlotta Stipa and Barbara Mostacci and Lara Alvisi and Paolo Tinuper and Francesca Bisulli",
note = "Ricercatori distaccati presso IRCCS a seguito Convenzione esclusiva con Universit{\`a} di Bologna (Licchetta Laura, Alvisi Lara, Tinuper Paolo, Bisulli Francesca)",
year = "2018",
month = "2",
day = "1",
doi = "10.1016/j.yebeh.2017.12.012",
language = "English",
volume = "79",
pages = "169--173",
journal = "Epilepsy and Behavior",
issn = "1525-5050",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Phenotype variability of GLUT1 deficiency syndrome

T2 - Description of a case series with novel SLC2A1 gene mutations

AU - Di Vito, Lidia

AU - Licchetta, Laura

AU - Pippucci, Tommaso

AU - Baldassari, Sara

AU - Stipa, Carlotta

AU - Mostacci, Barbara

AU - Alvisi, Lara

AU - Tinuper, Paolo

AU - Bisulli, Francesca

N1 - Ricercatori distaccati presso IRCCS a seguito Convenzione esclusiva con Università di Bologna (Licchetta Laura, Alvisi Lara, Tinuper Paolo, Bisulli Francesca)

PY - 2018/2/1

Y1 - 2018/2/1

N2 - Glucose transporter type 1 (GLUT1) deficiency due to SLC2A1 mutations causes a wide spectrum of neurologic disorders ranging from severe encephalopathy with developmental delay, epilepsy, ataxia, and acquired microcephaly to atypical less severe variants. Early diagnosis is crucial for prompt initiation of a ketogenic diet. Recognizing GLUT1 deficiency syndrome (GLUT1DS) may be challenging and results in delayed diagnosis. Here we describe the clinical and molecular findings of patients with SLC2A1 mutations referred to our adult Epilepsy Center. Patients with a clinical history suggestive of GLUT1DS were screened for SLC2A1 mutations. Blood samples were collected from probands and first-degree relatives. A lumbar puncture was performed in two patients in fasting state, and cerebrospinal fluid and blood glucose measurement were undertaken at the same time. Since 2010, 19 GLUT1DS probands have been screened for SLC2A1 mutations. We identified four different SLC2A1 mutations in three sporadic cases and one family. Three mutations (c.130_135delTACAAC, c.342_343insA, and c.845A > G) were novel, whereas one was previously reported in the literature associated with a different phenotype (c.497_499delTCG). Here we describe a small case series of patients with sporadic and familial GLUT1DS presenting with a broad phenotypic heterogeneity which is likely to be responsible for the considerable delay in diagnosis.

AB - Glucose transporter type 1 (GLUT1) deficiency due to SLC2A1 mutations causes a wide spectrum of neurologic disorders ranging from severe encephalopathy with developmental delay, epilepsy, ataxia, and acquired microcephaly to atypical less severe variants. Early diagnosis is crucial for prompt initiation of a ketogenic diet. Recognizing GLUT1 deficiency syndrome (GLUT1DS) may be challenging and results in delayed diagnosis. Here we describe the clinical and molecular findings of patients with SLC2A1 mutations referred to our adult Epilepsy Center. Patients with a clinical history suggestive of GLUT1DS were screened for SLC2A1 mutations. Blood samples were collected from probands and first-degree relatives. A lumbar puncture was performed in two patients in fasting state, and cerebrospinal fluid and blood glucose measurement were undertaken at the same time. Since 2010, 19 GLUT1DS probands have been screened for SLC2A1 mutations. We identified four different SLC2A1 mutations in three sporadic cases and one family. Three mutations (c.130_135delTACAAC, c.342_343insA, and c.845A > G) were novel, whereas one was previously reported in the literature associated with a different phenotype (c.497_499delTCG). Here we describe a small case series of patients with sporadic and familial GLUT1DS presenting with a broad phenotypic heterogeneity which is likely to be responsible for the considerable delay in diagnosis.

KW - Epilepsy

KW - Glucose transporter type I deficiency syndrome

KW - Nonepileptic paroxysmal phenomena

KW - SLC2A1 mutation

UR - http://www.scopus.com/inward/record.url?scp=85039989367&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85039989367&partnerID=8YFLogxK

U2 - 10.1016/j.yebeh.2017.12.012

DO - 10.1016/j.yebeh.2017.12.012

M3 - Article

C2 - 29306089

AN - SCOPUS:85039989367

VL - 79

SP - 169

EP - 173

JO - Epilepsy and Behavior

JF - Epilepsy and Behavior

SN - 1525-5050

ER -