Paroxysmal Events in Glut1 Deficiency

Background/Aim: Glut1 Deficiency (Glut1D) represents a rare metabolic encephalopathy with many faces. A defect in the facilitated glucose transporter GLUT1at the blood-brain barrier and in brain cells impairs cerebral glucose transport. Patients present with epilepsy, developmental delay, movement abnormalities or a complex combination of these features. Interestingly, paroxysmal non-epileptic events are reported with increasing age by parents and caretakers. To evaluate incidence, clinical characteristics, triggers, and associated features of paroxysmal events in pediatric Glut1D.

Methods: Sixty patients diagnosed with Glut1D were requested to provide videos of regular movement and paroxysmal episodes and to complete a questionnaire on paroxysmal events.

Results: Three videos illustrated the different character of paroxysmal episodes: ataxic-dystonic, choreatiform, and spastic-dystonic. Fifty-six of the 60 questionnaires were completed. Paroxysmal episodes occurred in 41/56 (73%) patients affecting motor control, tone, speech, and vigilance. Exercise, low ketosis, and sleep deprivation were identified as potential trigger factors. Episodes varied in time and were unrelated to gender, degree of hypoglycorrhachia, SLC2A1 mutations, or type of ketogenic diet treatment.

Conclusion: Paroxysmal nonepileptic events were reported as a major clinical feature in Glut1D (3 of 4 patients). They occur despite adequate ketogenic diet treatment, increase with age, and are triggered by low ketosis, sleep deprivation, and physical exercise. Our findings bridge the gap between pediatric Glut1D and Glut1D-associated exercise-induced paroxysmal dyskinesias described in adults.