At Baylor College of Medicine, Houston, and Columbia University Medical Center, New York, thirteen patients (11 male) with glucose transporter type 1 deficiency syndrome (Glut1-DS) but normal systemic carbohydrate homeostasis were studied to assess the effects of increased central nervous system glucose levels. Mean patient age was 14.2 years (range 6.5–32.9). CSF glucose was decreased in all patients with a mean of 32.5 mg/dl (range 16–39). Mutations in the GLUT1 gene (SLC2A1) were present in 11 patients. Twelve patients had seizures, mainly absence and myoclonic types, resistant to antiepileptic medication. Ataxia was present in 10, language delay in 10, microcephaly in 7, and motor delay in 5 patients. All patients had a full neuropsychological battery performed before a five-hour oral glucose tolerance test and during the test underwent repeated measures of attention, memory, fine-motor coordination, and well-being. Six patients also had prolonged EEG/video monitoring.
Following the glucose load, clinical seizures and EEG abnormalities decreased within the first 30 minutes and improvements lasted up to 180 minutes. Repeat psychological testing showed transient improvements in attention and motor coordination but verbal learning and memory performance failed to improve. Qualitative ratings of well-being improved from baseline and peaked at 180 minutes. Transient improvements in the EEG following glucose load included emergence of normal posterior alpha frequency, resolution of focal frontal and central slowing, and disappearance of interictal generalized spike-and-wave epileptiform discharges. However, the number of seizures and the interictal epileptiform discharges increased back toward baseline after 180 minutes.
The authors conclude that the transient clinical improvement following a glucose load in Glut1-DS patients confirms the pivotal role of GLUT1 in brain energy metabolism and the relation between low central nervous system glucose levels and the symptoms associated with Glut1-DS.
Although inherited metabolic disorders are a relatively rare cause of epilepsy in children, their early diagnosis is important. If untreated, they can lead to developmental delay or regression, mental retardation, movement disorders, and microcephaly or macrocephaly.1 Symptomatic epilepsies associated with a metabolic disorder in the infant or young child may imitate idiopathic generalized epilepsies but fail to respond to conventional antiepileptic medications.2
Glut1-DS is characterized clinically by infantile-onset seizures, acquired microcephaly, psychomotor retardation, choreoathetosis, dystonia, and ataxia.3 The seizures during infancy are frequently myoclonic and imitate benign myoclonic epilepsy. In early childhood, seizures resemble idiopathic absence epilepsy. Low CSF glucose (<40 mg/dl) is the diagnostic hallmark of Glut1-DS (40–50 mg/dl in milder cases).4 Ratio of CSF to blood glucose is a less reliable marker.4 Despite the importance of lumbar puncture in diagnosis of unexplained neurological disorders, most children with Glut1-DS do not undergo this test since fever is not a manifestation. Non-invasive gene sequencing for SLC2A1 mutations, an increasingly available test, may be preferred to...