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The role of SLC2A1 in early onset and childhood absence epilepsies

https://doi.org/10.1016/j.eplepsyres.2012.11.004Get rights and content

Summary

Early Onset Absence Epilepsy constitutes an Idiopathic Generalized Epilepsy with absences starting before the age of four years. Mutations in SLC2A1, encoding the glucose transporter, account for approximately 10% of EOAE cases. The role of SLC2A1 mutations in absence epilepsies with a later onset has not been assessed. We found two mutation carriers in 26 EOAE patients, while no mutations were found in 124 probands affected by CAE or JAE.

Introduction

Generalized Idiopathic Absences occur at different ages: Early Onset Absence Epilepsies (EOAE, age of onset <4 years), Childhood Absence Epilepsies (CAE, 4–10 years) and Juvenile Absence Epilepsies (JAE, >10 years). Within the generalized absence epilepsies, EOAE may represent a distinct subgroup. It has been shown that mutations in the SLC2A1 (solute carrier family 2 (facilitated glucose transporter), member 1) gene encoding the glucose transporter 1 (GLUT1) can be found in 10% of EOAE patients (Suls et al., 2009). GLUT1 is the main glucose transporter across the blood–brain barrier and in individuals with a GLUT1 defect a ketogenic diet can ameliorate not only seizures (De Vivo et al., 1991, Wang et al., 2005, Klepper et al., 2005, Coman et al., 2006) but also motor symptoms, especially dystonic and atactic features (Pons et al., 2010, Graham, 2011). Increase of seizures in fasting periods or aggravation of exercise induced motor symptoms is a typical sign for GLUT1 deficiency syndrome (Brockmann et al., 2001, Klepper et al., 2005). The aim of our study was to compare the role of SLC2A1 mutations in EOAE (cohort 1) and in absence epilepsies with later onset (cohort 2).

Section snippets

Cohorts

The study participants were recruited at the Clinic for Neuropaediatrics of Christian-Albrechts University in Kiel, Germany and the Danish Epilepsy Centre in Dianalund, Denmark. The Belgium probands were screened at the Department of Molecular Genetics, Antwerp, Belgium. Cohort 1 comprised 26 EOAE patients (18 German, 8 Danish) and cohort 2 consisted of 124 probands with CAE or JAE (25 German, 15 Danish, 84 Belgian). The second cohort was screened to determine the role of SLC2A1 mutations in

SLC2A1 in EOAE (cohort 1)

In a cohort of 26 EOAE patients we identified two probands of German descent with a mutation in the SLC2A1 gene.

Patient 1

The boy presented with first seizures at the age of 9 months. Typical absences were noticed at the age of 14 months. Dystonic movements and mild ataxia were described at the age of 4 years. Learning difficulties became obvious in childhood; the patient attended a school for intellectually disabled children. The EEG showed paroxysms of 3 Hz generalized spike-wave during absence seizures

Discussion

In our cohort of 26 EOAE patients, we identified two patients (2/26) with a SLC2A1 mutation and confirm the previously described frequency of 10% in EOAE (Suls et al., 2009).

In patient 1, the de novo SLC2A1 mutation was detected retrospectively at the age of 24 years when screening for SLC2A1 mutations in absence epilepsy patients with early onset. However, the aetiology was considered unknown throughout childhood and adolescence. Retrospectively, typical dystonic movements and fasting-related

Conclusion

We could confirm the important role of SLC2A1 mutations in EOAE, but mutations in this gene do not appear to play a major role in absence epilepsies beginning after the age of four. Clinicians might revisit the diagnosis of absence epilepsy with regard to the age of onset, particularly in cases with concomitant movement disorder. We hypothesize that, in analogy to patient 1 in our report, further patients with SLC2A1 mutations may as yet be undiagnosed and might benefit from treatment with the

Acknowledgements

We would like to thank all participating family members. This study was supported by the medical faculty of the Christian-Albrechts-University of Kiel and by the Peter and Jytte Wolf Foundation. The research was supported by the Fund for Scientific Research Flanders (FWO), Methusalem excellence grant of the Flemish Government, University of Antwerp, the Interuniversity Attraction Poles (IAP) program P6/43 of the Belgian Science Policy Office (BELSPO), and the Eurocores program EuroEPINOMICS of

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