The role of molecular analysis of SLC2A1 in the diagnostic workup of glucose transporter 1 deficiency syndrome

The study aimed to investigate the role of molecular analysis of SLC2A1 in the diagnostic workup of glucose transporter 1 deficiency syndrome (Glut1DS). During 2006-2020, we received 100 requests for SLC2A1 variant analysis of patients clinically suspected for Glut1DS. Pathogenic variants were detected in 37 patients, among whom 11 were familial cases. Most patients presented with epilepsy (n = 31; 84%), movement disorders (MD) (n = 28; 76%), and intellectual disabilities (ID) (n = 29; 78%). Moreover, paroxysmal dyskinesias (PD) (n = 10; 27%) were more frequently seen in familial cases (55%) than in sporadic cases (15%) (p < .05). The Glut1DS patients with ID typically had either epilepsy or MD. The presence of MD, particularly when associated with epilepsy or ID, indicated Glut1DS (p < .05). The cerebrospinal fluid (CSF) glucose levels were at or below the 10th percentile in all 32 SLC2A1-positive patients but only in 16 of 52 (31%) SLC2A1-negative patients (p < .05). Thus, CSF analysis is an essential tool in the diagnostic workup of Glut1DS. SLC2A1 molecular analysis should be performed in patients with a family history of Glut1DS or with at least one of the following clinical features, such as epilepsy, MD, and PD with or without ID, and low CSF glucose level. This would help in precise molecular diagnosis of the disease and facilitate effective treatment and appropriate genetic counseling.