br Treatment KD is currently the treatment of choice for

Treatment KD is currently the treatment of choice for GLUT1-DS. It is a high-fat, carbohydrate-restricted diet that mimics the metabolic state of fasting; so, the KD relies an exogenous rather than body fat for ketone production, thus maintaining ketosis without weight loss. As the developing brain requires substantially more energy in young children, the KD should be started as early possible whenever GLUT1-DS is suspected and should be continued at least until adolescence. In the vast majority of GLUT1-DS patients, seizure control by the classical 4:1 or 3:1 (fat:carbohydrate and protein) KD is imminent and efficient, and anticonvulsant therapy can be withdrawn. However, in a small number of patients, add-on anticonvulsants are needed. In a recent report, seizure control was rapid and impressive in eight patients, but only four could be weaned off anticonvulsants completely. In another study, seizures persisted in 1/15 patients despite anticonvulsants and adequate ketosis. Movement disorders, such as hypotonia, ataxia and dystonia are also positively affected by the KD,21, 27 while, the impact of KD on developmental delay appears less prominent. Recently, also the modified Atkins Diet has been used successfully in patients whit GLUT1-DS37, 60 and it may offers a good alternative in schoolchildren and adolescents, with difficulties maintaining a classical KD. KD is well tolerated and the compliance of patients generally is very good and side effects of KD are well known and very moderate.61, 62 Alpha-lipoic glycine transporter is discussed as alternative compound for treatment of GLUT1DS. Alpha-lipoic acid, an antioxidant, translocates intracellular pools of the insulin-sensitive GLUT4 transporter in muscle to the cell membrane, increasing the number of functional transporters; it is an approved drug for treating diabetic neuropathy and has also been used off label in several neurological conditions such as multiple sclerosis and Parkinson’s Disease. In GLUT1-DS alpha-lipoic acid supplementation was recommended based on the observation that it improves glucose transport in cultured muscle cells via mobilization of the GLUT4 transporter from intracellular pools. However, there is no convincing experimental evidence that this supplementation will have similar effects on the GLUT1 transporter at the blood–brain barrier and the available data on the effect of alpha-lipoic acid in GLUT1-DS are limited. Some pharmacological agents impair GLUT1 function and should be avoided; these substances include: ethanol, methylxanthines, caffeine, androgens, dioxine, tricyclic antidepressants and anticonvulsants such as phenobarbital, diazepam and valproate.
When should Glut-1 deficiency syndrome be suspected?
Introduction One of the hallmarks of cancer is its uncontrolled capacity for proliferation. To maintain increased proliferation, cancer cells have enhanced glucose metabolism [1]. Cancer cells prefer to convert glucose into lactate instead of using the oxidative phosphorylation chain for energy production, even in the presence of oxygen [1], [2]. This preferred conversion of glucose to lactate in the presence of oxygen is known as aerobic glycolysis or the Warburg effect. Glucose uptake across the plasma membrane is regarded as the rate-limiting step for glucose metabolism [3]. To reach a glycolytic rate that is almost 30-fold higher than normal, cancer cells take up glucose at an increased rate [3]. The transport of glucose across the cell membrane occurs via two types of transporters, glucose transporters (Gluts, solute carrier family 2, SLC2A) and sodium-dependent glucose cotransporters (SGLTs, solute carrier family 5, SLC5A). Gluts move glucose along a concentration gradient as facilitative transporters [4]. Conversely, SGLTs transport glucose into cells against the concentration gradient as active transporters [5]. In mammals, 14 Gluts have been identified and each exhibits different substrate specificities and tissue expression [6]. Glut1 is the most widely expressed transporter, and is involved in basal glucose uptake [4].