Glucose Transporter Type 1 (Glut1) Deficiency Syndrome Rare, But Treatable-Ketogenic Dietary Therapy as First-Line Therapy

Glut1 Deficiency Syndrome (Glut1-DS) is a rare metabolic disease that leads to complex encephalopathy. This is due to heterozygous, de novo mutations in theSLC2A1 gene in the majority of cases. The absence or reduced function of glucose transporter type 1 (GLUT1) causes an energy deficiency of the central nervous system (CNS), as not enough glucose is transported across the blood-brain barrier. The disease usually becomes apparent through cerebral seizures (such as absences or myoclonic-astatic seizures) in infancy and early childhood. Characteristic initial symptoms of the disease are also paroxysmal eye-head movements in infants. There is usually a global developmental impairment with a complex cerebral movement disorder; its main components are ataxia, dystonia, spasticity, and dysarthria. Some of the most severely affected patients develop secondary microcephaly. Some symptoms improve after meals because of the postprandial increase in the level of blood glucose. Symptoms are age related-in infancy and early childhood epilepsy is dominant, in adolescents and adults it is cerebral movement disorders. Diagnosis is based on: 1. typical clinical signs; 2. decreased CSF glucose in the presence of normoglycaemia; and 3. detection of a pathogenic variant of SLC2A1 gene. When Glut1-DS is strongly suspected or diagnosed, therapy must be initiated immediately to reach optimal cognitive development. As the CNS can use ketone bodies as an alternative source of energy instead of glucose, ketogenic dietary therapies (KDTs) are the treatment of choice. In the KDTs (classical ketogenic diet, modified Atkins diet), ketogenesis is induced by a high-fat and low-carbohydrate diet. Depending on the age of the patient, the compliance of the patient and his family, and the efficacy of the KDT, either the classic ketogenic diet or the Atkins diet is applied to achieve sufficient ketosis. The KDT should be continued at least until early adulthood.