Authors :
Heather Levine, RD – Orlando Health Medical Group
Kelly Urbanik, RD – Orlando Health Medical Group
Presenting Author: Stephanie Kyle, PhD – Acadia Pharmaceuticals Inc.
Vikram Prakash, MD – Orlando Health Medical Group
Rationale:
Rett syndrome (RTT) is a rare neurodevelopmental disease characterized by developmental regression, hand stereotypies, behavioral and communication issues, and impaired motor skills. Patients with RTT have multiple RTT-related comorbidities, including epilepsy, which occurs in approximately 60-90% of patients. In this population, seizures are primarily managed with pharmacologic therapy but non-pharmacologic options, such as ketogenic diet therapy, are common. Ketogenic diets are high fat, low carbohydrate, and moderate protein diets that promote ketosis to reduce seizures. When following a ketogenic diet, all sources of carbohydrates, including those from medications, must be accounted for. Trofinetide, which is the only approved treatment for RTT in patients aged ≥2 years in the US and patients aged ≥2 years weighing ≥9 kg in Canada, contains 0.03 grams of carbohydrates per 1 mL of medication. With recommended doses ranging from 25-60 mL twice daily, trofinetide may contribute 1.5-3.6 grams of carbohydrates per day toward a patient’s daily carbohydrate allowance. As such, the feasibility of maintaining ketosis through ketogenic diets while on trofinetide treatment is unknown.
Methods:
The cases presented are of 3 female patients with RTT receiving trofinetide for the treatment for their RTT symptoms who continued to experience suboptimal control of their comorbid seizures. For these patients, ketogenic diets were successfully started and maintained amid concomitant trofinetide therapy.Results:
Three female patients with RTT, aged 5-11 years, received trofinetide therapy, which was started at 10-15 mL BID and increased to 30-45 mL BID. The trofinetide doses contributed 0.6-0.9 grams and 1.8-2.7 grams of carbohydrates per day, respectively. All three patients had a history of intractable focal epilepsy with suboptimal seizure control despite multimodal antiseizure medication. As such, all three patients were initiated on ketogenic diets, with individualized net carbohydrate goals which ranged from 15-35 grams per day. In all three cases, ketosis was achieved and maintained amid concurrent trofinetide therapy, as evidenced by β-hydroxybutyrate levels ranging from 2.0-5.3 mmol/L. Subsequently, all 3 patients experienced improved seizure control while on ketogenic diets. Conclusions:
In these anecdotal cases, patients with RTT treated with trofinetide were successfully started and maintained on ketogenic diets to further optimize seizure control. All patients achieved ketosis, as evidenced by optimal β-hydroxybutyrate levels, and all patients experienced improved seizure control.
Funding:
No financial disclosures to report in the presentation of these cases.