Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/11639
Title: Glucose transporter 1 deficiency in the idiopathic generalized epilepsies.
Austin Authors: Arsov, Todor;Mullen, Saul A ;Rogers, Sue;Phillips, A Marie;Lawrence, Kate M;Damiano, John Anthony;Goldberg-Stern, Hadassa;Afawi, Zaid;Kivity, Sara;Trager, Chantal;Petrou, Steven;Berkovic, Samuel F ;Scheffer, Ingrid E 
Affiliation: Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Australia
Issue Date: 1-Nov-2012
Publication information: Annals of Neurology; 72(5): 807-15
Abstract: We examined whether glucose transporter 1 (GLUT1) deficiency causes common idiopathic generalized epilepsies (IGEs).The IGEs are common, heritable epilepsies that usually follow complex inheritance; currently little is known about their genetic architecture. Previously considered rare, GLUT1 deficiency, due to mutations in SLC2A1, leads to failure of glucose transport across the blood-brain barrier and inadequate glucose for brain metabolism. GLUT1 deficiency was first associated with an encephalopathy and more recently found in rare dominant families with epilepsy and paroxysmal exertional dyskinesia (PED). Five hundred four probands with IGEs and 470 controls underwent SLC2A1 sequencing. Glucose transport was assayed following expression of SLC2A1 variants in Xenopus oocytes. All available relatives were phenotyped, and SLC2A1 was sequenced.Functionally validated mutations in SLC2A1 were present in 7 of 504 (1.4%) probands and 0 of 470 controls. PED, undiagnosed prior to study, occurred in 1 proband and 3 of 13 relatives with mutations. The IGEs in probands and relatives were indistinguishable from typical IGE. Three cases (0.6%) had mutations of large functional effect and showed autosomal dominant inheritance or were de novo. Four (0.8%) cases had a subtle functional effect; 2 showed possible dominant inheritance, and 2 did not. These alleles leading to subtle functional impairment may contribute to complex, polygenic inheritance of IGE.SLC2A1 mutations contribute to approximately 1% of IGE both as a dominant gene and as a susceptibility allele in complex inheritance. Diagnosis of GLUT1 deficiency has important treatment (ketogenic diet) and genetic counseling implications. The mechanism of restricted glucose delivery differs from the current focus on IGEs as ion channel disorders.
Gov't Doc #: 23280796
URI: http://ahro.austin.org.au/austinjspui/handle/1/11639
DOI: 10.1002/ana.23702
URL: https://pubmed.ncbi.nlm.nih.gov/23280796
Type: Journal Article
Subjects: Adult
Aged
Animals
Carbohydrate Metabolism, Inborn Errors.complications.genetics
DNA Mutational Analysis
Epilepsy, Generalized.etiology.genetics
Evolution, Molecular
Female
Follow-Up Studies
Genotype
Glucose Transporter Type 1.deficiency.genetics
Humans
Male
Middle Aged
Monosaccharide Transport Proteins.deficiency.genetics
Mutation.genetics
Phenotype
Young Adult
Appears in Collections:Journal articles

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