Ketogenic Diet as an Epigenetic Therapy in SETD1B-Related Epilepsy

Ketone bodies, including butyrate, act as histone deacetylase inhibitors. We report a [VH2.1]4-year-old boy with SETD1B-related absence epilepsy, refractory to conventional medications, who achieved sustained >90% seizure reduction on the Modified Atkins ketogenic diet.

Single-cell RNA sequencing of 25,159 peripheral mononuclear cells across 3 samples: baseline, 3 months on-diet, and age-matched control, revealed widespread dysregulation of chromatin, ribosomal, immune, and mitochondrial pathways at baseline, which were reversed with ketogenic therapy. These findings suggest that the ketogenic diet can improve gene regulation in chromatin-mediated brain disorders.