Ketogenic Diet Shows Promise as Epigenetic Therapy for SETD1B Epilepsy

A team in Australia reported a detailed case in which a high-fat ketogenic diet produced sustained seizure control in a 4½-year-old boy with drug-refractory SETD1B (KMT2G) epilepsy. The case, published in Annals of Clinical and Translational Neurology, links the diet’s effects to potential epigenetic changes: single-cell blood analysis suggested reversal of widespread molecular abnormalities associated with the condition. The child had a de novo missense variant, classified as likely pathogenic, and experienced up to 30 atypical absence seizures daily from age 2½, plus later generalized tonic-clonic seizures. Standard medications including ethosuximide and sodium valproate failed, while lamotrigine stopped convulsive seizures. After starting a Modified Atkins ketogenic diet—carbohydrates initially limited to 15 grams per day, with fats providing 65% to 70% of energy—seizure control persisted over time.