Acute hyperglycemia produces transient improvement in glucose transporter type 1 deficiency.
OBJECTIVE
Glucose transporter type 1 deficiency syndrome (Glut1-DS) is characterized clinically by acquired microcephaly, infantile-onset seizures, psychomotor retardation, choreoathetosis, dystonia, and ataxia. The laboratory signature is hypoglycorrhachia. The 5-hour oral glucose tolerance test (OGTT) was performed to assess cerebral function and systemic carbohydrate homeostasis during acute hyperglycemia, in the knowledge that GLUT1 is constitutively expressed ubiquitously and upregulated in the brain.


METHODS
Thirteen Glut1-DS patients completed a 5-hour OGTT. Six patients had prolonged electroencephalographic (EEG)/video monitoring, 10 patients had plasma glucose and serum insulin measurements, and 5 patients had repeated measures of attention, memory, fine motor coordination, and well-being. All patients had a full neuropsychological battery prior to OGTT.


RESULTS
The glycemic profile and insulin response during the OGTT were normal. Following the glucose load, transient improvement of clinical seizures and EEG findings were observed, with the most significant improvement beginning within the first 30 minutes and continuing for 180 minutes. Thereafter, clinical seizures returned, and EEG findings worsened. Additionally, transient improvement in attention, fine motor coordination, and reported well-being were observed without any change in memory performance.


CONCLUSIONS
This study documents transient neurological improvement in Glut1-DS patients following acute hyperglycemia, associated with improved fine motor coordination and attention. Also, systemic carbohydrate homeostasis was normal, despite GLUT1 haploinsufficiency, confirming the specific role of GLUT1 as the transporter of metabolic fuel across the blood-brain barrier. The transient improvement in brain function underscores the rate-limiting role of glucose transport and the critical minute-to-minute dependence of cerebral function on fuel availability for energy metabolism.
Akman
Cigdem I
CI
Department of Neurology, Baylor College of Medicine, Houston, TX, USA.
Engelstad
Kristin
K
Hinton
Veronica J
VJ
Ullner
Paivi
P
Koenigsberger
Dorcas
D
Leary
Linda
L
Wang
Dong
D
De Vivo
Darryl C
DC
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D001786:Blood Glucose; D001921:Brain / Q000503:physiopathology; D002648:Child; D005260:Female; D005951:Glucose Tolerance Test; D051272:Glucose Transporter Type 1 / Q000172:deficiency*; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D008297:Male; D009483:Neuropsychological Tests; D011446:Prospective Studies; D012640:Seizures / Q000097:blood / Q000503:physiopathology*; D013577:Syndrome; D013997:Time Factors; D055815:Young Adult
D001786:Blood Glucose; D051272:Glucose Transporter Type 1; D007328:Insulin