GLUT1 deficiency syndrome (Glut1-DS) is a rare genetic disorder caused by mutations in the SLC2A1[BMHS1.1] gene, which encodes the glucose transporter type 1 (GLUT1). This transporter moves glucose across the blood-brain barrier, supplying the brain with its main source of energy. When glucose transport is reduced, the brain may rely on ketone bodies—an alternative fuel that the body naturally produces during prolonged fasting—to meet its energy needs.
Because of this energy shortage, patients often experience neurological symptoms from early brain development onwards. These symptoms can vary widely and may change over time.

Table of contents

Symptoms

In childhood:

  • Developmental delay (slow acquisition of skills such as walking, talking, and learning; may progress to mild-to-severe intellectual difficulties)
  • Seizures (often starting in infancy, sometimes resistant to medication, and may decrease with age)
  • Acquired microcephaly (head size smaller than expected, developing after birth)

In adolescence and adulthood:

  • Movement disorders, such as:
    • Ataxia (clumsiness or poor coordination)
    • Dystonia (involuntary muscle contractions or abnormal postures)
    • Dysarthria (slurred or slow speech)
    • Exercise- or stress-induced paroxysmal dyskinesias (sudden, temporary abnormal movements triggered by physical activity, fasting, or stress)
  • Cognitive difficulties of varying severity (often mild to moderate)
  • Migraines, sometimes with temporary weakness or numbness in one or more limbs.

Brain MRI often provides limited diagnostic guidance.

 

Cause

Glut1-1DS is caused by pathogenic variants in the SLC2A1 gene, which encodes the glucose transporter type 1. Most cases arise from de novo variants, occurring spontaneously without a family history. However, autosomal dominant inheritance is well described, with affected individuals transmitting the condition to their offspring, sometimes with variable severity.

In addition, mosaicism has increasingly been recognized. In these cases, the pathogenic variant is present in only a proportion of cells due to a post-zygotic event. Mosaicism may result in milder or atypical clinical presentations and can complicate genetic diagnosis, particularly when the variant is present at low levels in blood.

Diagnosis is based on clinical features and laboratory tests:

  • Lumbar puncture often shows low glucose levels in cerebrospinal fluid compared to blood (relative hypoglycorrhachia)
  • MetaGlut1 (e. available in France) may reveal reduced GLUT1 expression on red blood cells
  • Genetic testing confirms a pathogenic mutation in the SLC2A1 gene.

 

Treatment

Treatment focuses on providing the brain with alternative energy sources:

  • Ketogenic diet: A high-fat, low-carbohydrate, moderate-protein diet that reduces glucose use and promotes ketone production as fuel for the brain. Dietitians specialized in inherited metabolic disorders carefully manage the diet, which is particularly effective at controlling seizures.
  • Triheptanoin: A specially formulated medium-chain triglyceride (MCT) with an odd number of carbons that provides 2 intermediates to the Krebs cycle, thereby providing an alternative source of energy to the brain. Clinical studies show it can help especially patients with movement disorders.

Schéma - Syndrome et deficit en glut1