back to the list

GLUT1-Deficiency Syndrome - GLUT1

Clinical Features

GLUT1 Deficiency Syndrome is caused by mutations of the SLC2A1 gene. Diagnosis is important because it represents a potentially treatable genetic disorder. Patients can present with various complex clinical phenotypes:

• infantile seizures refractory to anticonvulsants: Seizures usually begin between age one and four months. Apneic episodes and abnormal episodic eye movements simulating opsoclonus may precede the onset of seizures by several months. Various seizure types and varying degrees of cognitive impairment, ranging from learning disabilities to severe intellectual disability, are observed. Additional neurological symptoms - like spasticity, ataxia, dystonia, and other paroxysmal neurologic phenomena - may develop. Symptoms often worse in the morning or prior to meals. Deceleration of head growth is frequent.

• absence epilepsy: GLUT1 deficiency may be an important monogenic cause of absence epilepsies with onset from early childhood to adult life. Subtle paroxysmal exertional dyskinesia may be a helpful diagnostic clue in some patients.

• paroxysmal exertion-induced dyskinesia (PED) has been described as phenotype of SLC2A1-mutations, some patients have been diagnosed as adults.

The phenotypic spectrum has broadened since SLC2A1 mutations have been described in patients with additional neurological symptoms or paroxysmal events like alternating hemiplegia, ataxia, dystonia or complex movement disorders have been described. Concomitant epilepsy is not mandatory. The phenotype may vary even within families carrying the same mutation.

GLUT1 deficiency syndrome is caused by impaired glucose transport into brain. The diagnosis is established by a low ratio of CSF glucose concentration to blood glucose concentration( <0,45) with low-to-normal lactat levels. Most patients can be effectively treated by a ketogenic diet with ketones serving as alternative energy supply.

Genetic Information

The GLUT1 (SLC2A1) gene encodes the specific glucose transporter in brain, placenta, and erythrocytes. The gene consists of 10 exons und is localized on  chromosome 1p35-p31.3. The majority of mutations are autosomal dominant and frequently occur de novo. Autosomal recessive inheritance has also been reported in single cases.

Diagnostic