Diagnostic Challenges Associated with GLUT1 Deficiency: Phenotypic Variabilities and Evolving Clinical Features

Yonsei Med J. 2019 Dec;60(12):1209-1215. doi: 10.3349/ymj.2019.60.12.1209.

Abstract

GLUT1 deficiency is a rare neurometabolic disorder that can be effectively treated with ketogenic diet. However, this condition is underdiagnosed due to its nonspecific, overlapping, and evolving symptoms with age. We retrospectively reviewed the clinical course of nine patients diagnosed with GLUT1 deficiency, based on SLC2A1 mutations and/or glucose concentration in cerebrospinal fluid. The patients included eight boys and one girl who initially presented with seizures (44%, 4/9) or delayed development (44%, 4/9) before 2 years of age, except for one patient who presented with apnea as a neonate. Over the clinical course, all of the children developed seizures of the mixed type, including absence seizures and generalized tonic-clonic seizures. About half (56%, 5/9) showed movement disorders such as ataxia, dystonia, or dyskinesia. We observed an evolution of phenotype over time, although this was not uniform across all patients. Only one child had microcephaly. In five patients, ketogenic diet was effective in reducing seizures and movement symptoms, and the patients exhibited subjective improvement in cognitive function. Diagnosing GLUT1 deficiency can be challenging due to the phenotypic variability and evolution. A high index of clinical suspicion in pediatric and even older patients with epilepsy or movement disorders is key to the early diagnosis and treatment, which can improve the patient's quality of life.

Keywords: GLUT1 deficiency; SLC2A1; ketogenic diet; phenotypic variability.

MeSH terms

  • Adolescent
  • Adult
  • Biological Variation, Population*
  • Carbohydrate Metabolism, Inborn Errors / diagnosis*
  • Carbohydrate Metabolism, Inborn Errors / diagnostic imaging
  • Carbohydrate Metabolism, Inborn Errors / pathology*
  • Child
  • Child, Preschool
  • Female
  • Glucose Transporter Type 1 / genetics
  • Humans
  • Infant
  • Infant, Newborn
  • Magnetic Resonance Imaging
  • Male
  • Monosaccharide Transport Proteins / deficiency*
  • Phenotype
  • Quality of Life
  • Retrospective Studies

Substances

  • Glucose Transporter Type 1
  • Monosaccharide Transport Proteins
  • SLC2A1 protein, human

Supplementary concepts

  • Glut1 Deficiency Syndrome