Abstracts

Rationale: Glucose-transporter type 1 deficiency syndrome (GLUT1 DS) is a metabolic disorder characterized by impaired glucose transport across the blood brain barrier. GLUT1 DS presents with variable clinical manifestations including seizures, movement disorders, and cognitive impairment. The recommended first line therapy is a ketogenic diet (KD), which provides ketones as fuel for the brain, bypassing the metabolic defect. Consensus recommendations suggest the classic ketogenic diet (CKD) in young children and the Modified Atkins ketogenic diet (MAD) in those of school age. There are no studies directly comparing efficacy of the two diets. At our institution, children with GLUT1 DS are prescribed the medium-chain triglyceride ketogenic diet (MCTKD). The MCTKD allows for more carbohydrate and less fat intake, which improves meal-planning choices and this flexibility may improve adherence.  Here, we describe the experience of children with GLUT1DS treated with MCTKD. Methods: Data was collected from an ongoing prospective study of children initiating diet therapy after September 1, 2013 at the Hospital for Sick Children in Toronto, Canada. Children with genetically confirmed GLUT1 DS were included in this analysis. Parent report of seizure frequency and clinical manifestations of GLUT1 DS were collected at baseline and 6 months after diet initiation and compared. Results: Seven children with GLUT1 DS were identified. Of the 7 children, the median age at diet initiation was 8.5 years (range: 4.0-11.7 years), and 6 were males (86%). More than half (57%) had seizures at baseline, and (71%) had a movement disorder. At 6-month follow-up, 2 children had no clinical seizures, 1 had > 90% seizure reduction, and 1 had no change. Six children had cognitive improvement reported by family and movements improved in four. Reported side effects included mild constipation (2/8), diarrhea (3/8) and vomiting (2/8) which all resolved. In two cases, there was difficulty with diet adherence. One child had incomplete diet implementation. During the first 3 months, ketosis was seldom achieved. By 6 months, ketosis was achieved but adherence remained variable, and this child had no improvement in seizure frequency. A second child started the diet and improvements in cognition were noted at six-month follow-up; however, maintaining the diet was not feasible due to social circumstances, and the diet was discontinued. Conclusions: The MCTKD may be an effective treatment for seizures, cognitive, and motor manifestations of GLUT1 DS. The diet was tolerated with no major side effects. There was a 71% diet adherence rate in the cohort analyzed. Further research is necessary to understand whether MCTKD and other KDs have equivalent therapeutic effects, and how to best support GLUT1 DS families in implementing/maintaining a KD.  Funding: Sponsored by OBI