Abstracts

Rationale: We recently demonstrated that over 10% (4/32) of a cohort with Early-Onset Absence Epilepsy (EOAE) had SLC2A1 mutations leading to GLUT1-deficiency, an autosomal dominant condition with a specific and effective therapy (ketogenic diet). In this study, we sought to replicate this finding and thereby to confirm that mutational analysis of SLC2A1 for the treatable metabolic condition GLUT1-deficiency is a useful diagnostic test in EOAE. Methods: EOAE was defined as epilepsy of unknown cause with predominantly absence seizures, generalised spike wave (>2.5Hz) and onset under 4 years. Those with tonic or atonic seizures were excluded. A total of 40 new cases underwent SLC2A1 mutational analysis by direct sequencing. Results: 10% (4/40) of our new cases with EOAE had missense mutations in SLC2A1 resulting in GLUT1 deficiency. All changes were either affecting an evolutionary conserved amino acid (Leu159Arg, Leu169Pro, Leu215Phe) or affected both amino acid polarity and charge (Leu159Arg, Gly53GluAll patients had intellect within the normal range, although learning difficulties were present in one and another had a diagnosis of autism spectrum disorder. Seizures were refractory in 1 case. Conclusions: This study replicates our previous finding that over 10% of EOAE is due to GLUT1-deficiency in an independent cohort. We have now identified a total of 8 EOAE cases with SLC2A1 mutations in a total of 72 EOAE patients screened to date. Given the major treatment and genetic counselling implications, SLC2A1 mutational analysis should be part of the routine diagnostic work-up for EOAE.