Glut1 Deficiency Syndrome (Glut1DS): State of the art in 2020 and recommendations of the international Glut1DS study group

Abstract

Glut1 deficiency syndrome (Glut1DS) is a brain energy failure syndrome caused by impaired glucose transport across brain tissue barriers. Glucose diffusion across tissue barriers is facilitated by a family of proteins including glucose transporter type 1 (Glut1). Patients are treated effectively with ketogenic diet therapies (KDT) that provide a supplemental fuel, namely ketone bodies, for brain energy metabolism. The increasing complexity of Glut1DS, since its original description in 1991, now demands an international consensus statement regarding diagnosis and treatment. International experts (n = 23) developed a consensus statement utilizing their collective professional experience, responses to a standardized questionnaire, and serial discussions of wide‐ranging issues related to Glut1DS. Key clinical features signaling the onset of Glut1DS are eye‐head movement abnormalities, seizures, neurodevelopmental impairment, deceleration of head growth, and movement disorders. Diagnosis is confirmed by the presence of these clinical signs, hypoglycorrhachia documented by lumbar puncture, and genetic analysis showing pathogenic SLC2A1 variants. KDT represent standard choices with Glut1DS‐specific recommendations regarding duration, composition, and management. Ongoing research has identified future interventions to restore Glut1 protein content and function. Clinical manifestations are influenced by patient age, genetic complexity, and novel therapeutic interventions. All clinical phenotypes will benefit from a better understanding of Glut1DS natural history throughout the life cycle and from improved guidelines facilitating early diagnosis and prompt treatment. Often, the presenting seizures are treated initially with antiseizure drugs before the cause of the epilepsy is ascertained and appropriate KDT are initiated. Initial drug treatment fails to treat the underlying metabolic disturbance during early brain development, contributing to the long‐term disease burden. Impaired development of the brain microvasculature is one such complication of delayed Glut1DS treatment in the postnatal period. This international consensus statement should facilitate prompt diagnosis and guide best standard of care for Glut1DS throughout the life cycle.

Classic Ketogenic Diet and Modified Atkins Diet in SLC2A1 Positive and Negative Patients with Suspected GLUT1 Deficiency Syndrome: A Single Center Analysis of 18 Cases

“…The current standard treatment for GLUT1DS are the KDT, especially the CKD [ 4 , 6 , 12 , 19 , 20 ]. Recent reviews have reported that 60% of the patients were seizure-free after the implementation of the diet, and 80% of patients with movement disorders improved [ 3 , 13 ].…”

“…The current gold standard treatment for GLUT1DS are ketogenic dietary therapies (KDT), especially the classic ketogenic diet (CKD) [ 6 ]. CKD is a high fat and low carbohydrate diet that provides ketones as an alternative fuel to the brain.…”

The Implementation Science for Genomic Health Translation (INSIGHT) Study in Epilepsy: Protocol for a Learning Health Care System

“…In vitro, Na+ current blockers decrese ubnormal ionic currants resulting from SCN1A mutations [60,61]. First line treatment is ketogenic diet [71].…”

Metabolic Control of Epilepsy: A Promising Therapeutic Target for Epilepsy

“…Ketogenic diet therapy is the gold standard treatment for patients with GLUT1 deficiency syndrome ( 57 ). The age at the correct diagnosis is the most important factor determining prognosis, and early diagnosis is very important as well as initiating the ketogenic diet as soon as possible ( 58 ).…”