Compatibility of trofinetide with ketogenic diets in patients with rett syndrome: case reports

Rett syndrome (RTT) is a rare neurodevelopmental disease characterized by developmental stagnation and regression. Epilepsy is seen in 60–80% of patients with RTT. Seizures are primarily managed with pharmacologic therapy; although ketogenic diets can be used to further optimize seizure control in patients with drug-resistant epilepsy. When following a ketogenic diet, all sources of carbohydrates must be considered. Trofinetide, an approved treatment for RTT, is available as trofinetide oral solution (TOS; marketed as DAYBUE®) and trofinetide powder for oral solution (TPOS; marketed as DAYBUE® Stix). TOS contributes 0.03 g of carbohydrates/mL of oral solution while TPOS contributes 0.04 g of carbohydrates/g of powder. Across recommended doses, TOS contributes 1.5–3.6 g of carbohydrates/day and TPOS contributes 0.40–0.96 g of carbohydrates/day. The feasibility implementing a ketogenic diet while taking trofinetide is unknown. Here, we present cases of patients with RTT who were started and maintained on ketogenic diets amid concomitant TOS before TPOS was available. This suggests that TOS is compatible with ketogenic diets in patients with RTT. TPOS should also be compatible with ketogenic diets, as it contains less carbohydrates per dose than TOS. More research is needed to confirm the compatibility of trofinetide formulations with ketogenic diets.