Glucose Transporter Type 1 Deficiency Syndrome

Glucose Transporter Type 1 Deficiency Syndrome

Glucose transporter type 1 deficiency syndrome (GLUT1-DS) is a rare genetic disease that impairs the normal transport of glucose from the blood to the brain, resulting in the absence or severe reduction of glucose in the brain, leading to severe cerebral consequences. GLUT1 deficiency syndrome is a genetically determined neurological disorder caused by insufficient glucose transport into the brain. This transport defect results in low glucose levels in the brain, leading to reduced energy availability for nerve cells, and is due to a mutation in the SLC2A1 gene, which is currently the only known gene associated with this condition.

The condition is also known as De Vivo disease, named after the physician who discovered it in the USA in 1991, describing for the first time an early-onset epileptic encephalopathy in which a decrease in glucose in the cerebrospinal fluid was observed. De Vivo treated these children with the ketogenic diet, achieving good results. However, to date, the disease has been described in very different clinical situations from those initially identified and with varied symptoms. Moreover, while cases were once very rare, the number of identified patients is now significantly increasing, thanks to greater awareness of the disease compared to the past and the more widespread use of genetic testing. However, it is believed that the number of cases is still underestimated, both because it is not a disease known to everyone and because it is often confused with epilepsy (which is one of the symptoms). The epidemiology is still unknown, but in Italy, there are estimated to be between 300 and 400 pediatric patients, although in reality, the patients with confirmed diagnoses are fewer than 200.

The syndrome presents a wide clinical spectrum that usually includes cognitive disability, epilepsy, exercise-induced paroxysmal dyskinesia, acquired microcephaly, hemolytic anemia, gait disturbances, and dyspraxia in various combinations. However, there are other clinical manifestations that we consider equally peculiar but have so far been insufficiently described and not interpreted as related to the syndrome. In reality, there is a great variability in symptoms and severity of the disease: there are people who have significant cognitive delays and others who lead completely normal lives. I have known families with apparently healthy grandparents or parents or with modest cognitive or motor delays, despite being affected by the syndrome, and grandchildren and children with much more complex symptoms and disorders.

Currently, there is no medical therapy but only dietary therapy, through the ketogenic diet. Patients with GLUT1-DS must start this diet as soon as possible to prevent and treat the pathological manifestations of the syndrome and then continue it for life. This diet, through the production of ketone bodies, provides the necessary energy to the brain in the absence of sugars. The diet intervenes in the metabolic disorder and allows for effective treatment of epileptic seizures and movement disorders, while the results for cognitive deficit are variable. It is an unbalanced diet, with a high fat content and very low in proteins, carbohydrates, and glucose, and although it has been known for a hundred years, it has always been used very little in Italy because it is the opposite of the Mediterranean diet. In practice, a large amount of fatty foods is consumed to induce chronic ketosis (or chronic acetone), which leads to high ketone production, providing the brain with the energy it lacks.

However, this type of diet is extremely complex, and the diet, strictly personalized, must be carefully planned by a team of expert specialists and must be carried out under the supervision of specialized reference teams.




Prof. Pierangelo Veggiotti – Full Professor