The role of SLC2A1 mutations in myoclonic astatic epilepsy and absence epilepsy, and the estimated frequency of GLUT1 deficiency syndrome

Abstract

SUMMARYThe first mutations identified in SLC2A1, encoding the glucose transporter type 1 (GLUT1) protein of the blood-brain barrier, were associated with severe epileptic encephalopathy. Recently, dominant SLC2A1 mutations were found in rare autosomal dominant families with various forms of epilepsy including early onset absence epilepsy (EOAE), myoclonic astatic epilepsy (MAE), and genetic generalized epilepsy (GGE). Our study aimed to investigate the possible role of SLC2A1 in various forms of epilepsy including MAE and absence epilepsy with early onset. We also aimed to estimate the frequency of GLUT1 deficiency syndrome in the Danish population. One hundred twenty patients with MAE, 50 patients with absence epilepsy, and 37 patients with unselected epilepsies, intellectual disability (ID), and/or various movement disorders were screened for mutations in SLC2A1. Mutations in SLC2A1 were detected in 5 (10%) of 50 patients with absence epilepsy, and in one (2.7%) of 37 patient with unselected epilepsies, ID, and/or various movement disorders. None of the 120 MAE patients harbored SLC2A1 mutations. We estimated the frequency of SLC2A1 mutations in the Danish population to be approximately 1:83,000. Our study confirmed the role of SLC2A1 mutations in absence epilepsy with early onset. However, our study failed to support the notion that SLC2A1 aberrations are a cause of MAE without associated features such as movement disorders.

A 23 years follow-up study identifies GLUT1 deficiency syndrome initially diagnosed as complicated hereditary spastic paraplegia

“…However, the new study was carried out only recently, allowing a long follow up in different generations. This is in line with a recent study suggesting that GLUT1DS is underdiagnosed, and its frequency in certain populations may reach to about 1:83,000e1:90,000 (Coman et al, 2006;Larsen et al, 2015). The classical phenotype of GLUT1DS is characterized by infantile seizures (resistant to traditional seizure medications), developmental delay, acquired microcephaly and complex movement disorders consisting of ataxia, dystonia and spasticity, more often paroxystic.…”

Dysfunction of the Cerebral Glucose Transporter SLC45A1 in Individuals with Intellectual Disability and Epilepsy

“…The phenotypic spectrum of GLUT1 transporter deficiency has expanded with the recognition of variants causing, for example, predominant ataxia or dystonia without seizures, paroxysmal exercise-induced dyskinesia with or without epilepsy, and a spectrum of epilepsy syndromes such as early-onset absence epilepsy, myoclonic astatic epilepsy, focal seizures, and infantile spasms. 16 (also see GeneReviews in the Web Resources). Our affected individuals share clinical features associated with the GLUT1-deficiency phenotype, such as focal epilepsy and developmental delay or ID; however, they lack many features associated with the classic GLUT1 deficiency (such as a dystonia, ataxia, and microcephaly) or non-classic GLUT1-deficiency phenotype (such as paroxysmal movement disorder, early-onset absence epilepsy, or myoclonic astatic epilepsy).…”

A Data Fusion Approach to Enhance Association Study in Epilepsy

“…Excluding PLCB1 (contained in hsa04919), this gene group can embed some small signal. Further analysis conducted on ATP1A2, SLC2A1, SLC2A2 KCNMA1 and KCNN3 showed they all are related to epilepsy or seizures [38, 39, 56, 57]. …”