J Korean Child Neurol Soc.  2007 Nov;15(2):131-141.

Glucose Transporter Type 1 Deficiency Syndrome

• Kim SK

Abstract

D-glucose is an essential fuel for metabolism in mammalian cells and the predominant fuel source for the brain. Transport of glucose across tissue barriers is mediated by stereospecific transporter proteins. Glut-1 is a major glucose transporter expressed on vascular endothelial cells comprising the blood brain barrier and is responsible for glucose entry into the brain. Impaired glucose transport across the blood brain barrier results in Glut-1 deficiency syndrome(DS). It is caused by haploinsufficiency of the blood brain barrier hexose carrier. Heterozygous mutations or hemizygosity of the GLUT-1 gene cause Glut-1 DS. It is characterized by infantile seizures refractory to anticonvulsants, developmental delay, acquired microcephaly, spasticity, ataxia, opsoclonus and other paroxysmal neurological phenomena, often occurring prior to meals. The diagnosis of Glut-1 DS is established in neurologically impaired patients with reduced cerebrospinal glucose concentration(hypoglycorrhachia) and lactate concentration in the absence of hypoglycemia. Decreased 3-O-methyl-D-glucose uptake in erythrocytes also supports the diagnosis of Glut-1 DS. Several treatment strategies have been pursued, none optimal, as it relates to the developmental encephalopahty associated with this clinical syndrome. Ketogenic diet has been effective in controlling seizures but has had little measurable effects on the associated cognitive impairments and behavioral disturbance. Current treatment is inadequate, and future studies should be directed at the mechanisms designed to upreglulate GLUT-1 expression, thereby increasing residual Glut-1 activity to 75 to 100%.

Keyword

Glut-1 deficiency syndrome; Epilepsy; Hypoglycorrhachia

MeSH Terms

3-O-Methylglucose
Anticonvulsants
Ataxia
Blood-Brain Barrier
Brain
Diagnosis
Endothelial Cells
Epilepsy
Erythrocytes
Glucose Transport Proteins, Facilitative*
Glucose Transporter Type 1*
Glucose*
Haploinsufficiency
Humans
Hypoglycemia
Ketogenic Diet
Lactic Acid
Meals
Metabolism
Microcephaly
Muscle Spasticity
Ocular Motility Disorders
Seizures
3-O-Methylglucose
Anticonvulsants
Glucose
Glucose Transport Proteins, Facilitative
Glucose Transporter Type 1
Lactic Acid