Efficacy of the Ketogenic Diet as Targeted Therapy in a Cohort of Patients with GLUT1-DS

OBJECTIVES Glucose transporter type 1 deficiency syndrome (GLUT1-DS) is a neurometabolic disorder due to pathogenic variants in the SLC2A1 gene, which determine altered glucose entrance into the central nervous system, leading to drug-resistant epilepsy, developmental delay, acquired microcephaly, and movement disorders. Ketogenic diet (KD) is known to be the target therapy for this condition. In this study we report on a cohort of GLUT1-DS patients treated with KD. METHODS We performed a retrospective study collecting data from a cohort of 35 patients diagnosed with Glut1 deficiency syndrome. We collected demographic, genetic, and baseline clinical data before the initiation of the ketogenic diet, followed by longitudinal assessments of neurological clinical status, neuropsychological parameters, quality of life, and electroencephalographic changes at various annual time points. RESULTS Thirty-five patients were included, with a median age of 13.5 years (range: 4 months – 42 years). The median age at clinical onset was 22.5 months. All were started on KD, but six interrupted the treatment because of poor family compliance and difficulty with KD management. Among those who underwent the KD, the median follow-up time was 4.25 years (range 1-12 years). Epilepsy was reported in 28/29 (96.5%) and 18/29 (62%) reached seizure freedom after the KD start, 4/29 (13.8%) had >50% seizure reduction. Fourteen patients (48%) presented a movement disorder (encompassing paroxysmal exercise-induced dyskinesia, choreoathetosis, abnormal eyes movements); 4/29 (13.8%) presented ataxia. After KD treatment, 6/29 (20.7%) no more presented paroxysmal movement disorders. Fourteen/29 (48.3%) had intellectual disability, severe (14.3%), moderate (35.7%), mild (50%), one had borderline intellectual functioning. No severe adverse events were reported. CONCLUSION We report detailed follow-up of a cohort of GLUT1-DS patients, emphasizing its safety and effectiveness in controlling epileptic seizures and movement disorders.