Glucose transporter type 1 deficiency: a study of two cases with video-EEG

Abstract

Glucose transporter type 1 (GLUT1) deficiency is an inborn error of glucose transport. Clinical manifestations are presumed secondary to reduced glucose transport across the blood brain barrier, and include seizures, abnormal tone, developmental delay and hypoglycorrhachia. A high index of suspicion is important as GLUT1 deficiency is a potentially treatable cause of mental retardation. We studied two affected children by continuous video-EEG in order to better understand the cause of the clinical manifestations and improvement on a ketogenic diet. The EEG was characterized by generalized paroxysmal 2-2.5 Hz spike-wave discharges, although normal EEGs were also obtained. Atypical absence seizures were the most prominent clinical seizure. Epileptiform activity and clinical seizures occurred in both children while acutely ketotic and non-ketotic, but were markedly more frequent in one child when non-ketotic. Discharges were not associated with a reduction in substrate for brain metabolism in the blood at that time. Conclusion Atypical absence seizures are common in glucose transporter type 1 deficiency and should alert the clinician to the possibility of this treatable disorder when present in a young child with developmental delay. Our data suggest that the therapeutic mechanism of the ketogenic diet in this disorder is more complicated than simply delivering ketones as an alternative substrate for brain metabolism.

Facilitated glucose transporter protein type 1 (GLUT1) deficiency syndrome: impaired glucose transport into brain – a review

“…Interestingly, Korenke et al [7] observed that epileptical discharges and slowing of background activity recorded in two patients in the fasting state were fully reversible following food intake. This reflects the clinical observation that seizure activity and motor deficits in some patients clearly increase in the fasting state [6,8]. Based on this observation we suggest an EEG following a 12-18 h fast and a post-prandial EEG.…”

“…To date, 24 patients with GLUT1 deficiency syndrome have been published [6,8,16,17,43,46,70,83] and several additional cases described in abstract form [38,39,40,45,62]. In general, the clinical presentation is heterogeneous and often unspecific.…”

“…Preliminary results indicate that in infancy, behavioural arrest seizures might be associated with focal temporal and posterior spikes, whereas later in childhood mixed motor seizures might be associated with generalised spike-wave discharges [39]. A study of two patients with atypical absence seizures reported generalised paroxysmal 2-2.5 Hz spike-wave discharges, although normal EEGs were also obtained [6]. Interestingly, Korenke et al [7] observed that epileptical discharges and slowing of background activity recorded in two patients in the fasting state were fully reversible following food intake.…”

“…Episodes of slowed mental perception, unsteady gait, and slurred speech are often described as a ''drunken appearance''. They are frequently observed in the morning and in other preprandial settings and resolve with food intake [6,8,43]. The heterogeneous clinical features suggest several subtypes of this disorder that have not yet been characterised.…”

GLUT1 deficiency syndrome – 2007 update

“…In some patients symptoms and EEG abnormalities can be aggravated by fasting and reversed by food intake. 27,[55][56][57] Thus, EEG recordings in preprandial (12-18h fast) and postprandial settings can be of some diagnostic value. Ictal EEG features have been characterized as focal slowing or epileptiform discharges in infants and generalized 2.5-4Hz spike-wave patterns in children.…”