Failure of ketogenic diet therapy in GLUT1 deficiency syndrome

Purpose: Epilepsy in GLUT1 deficiency syndrome is generally drug-resistant; ketogenic diet (KD) therapy is the mainstay of therapy, as production of ketones provides the brain with an alternative energy source, bypassing the defect in GLUT1. Failure of KD therapy and risk factors for failure have been sparsely published. Methods: We performed a retrospective study of GLUT1DS patients with refractory epilepsy failing on KD therapy, to identify their clinical characteristics. Results: Failure of the ketogenic diet was due to KD inefficacy (poor effect despite adequate ketosis), as well as intolerance and an inability to attain ketosis. Our cohort of seven patients in whom KD therapy failed stood out for their advanced age at seizure onset, i.e. almost 4 years vs 8 months in large series, female sex, as well as their advanced age at diagnosis and initiation of KD therapy. EEG recordings during KD therapy can aid in the assessment of effectiveness of the KD therapy. Conclusions: GLUT1DS is generally described as a treatable disorder and existing case series do not provide details of treatment failure. In select patients with GLUT1DS, KD therapy fails, rendering GLUT1DS an essentially untreatable disorder. Failure of the ketogenic diet was due to KD inefficacy (poor effect despite adequate ketosis), as well as intolerance and an inability to attain ketosis. Failure to reduce seizure frequency with deterioration of the EEG findings should lead to consideration of cessation of KD therapy. (C) 2019 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.