Abstracts

Rationale: Mutations in the SLC13A5 gene, a citrate transporter, causes a rare autosomal recessive epilepsy syndrome typically beginning with seizures in the neonatal period. Lifelong motor difficulties, cognitive impairment and epilepsy has been described in several retrospective cohorts. The TESS Research Foundation funded a prospective international natural history and biomarker discovery study to increase the success of future clinical trials. The initial visit data from the cohort of 16 patients, from (Belgium, Brazil, Canada, Spain, Iceland, Romania and UK) are reported here.

Methods: The TESS Research Foundation helped to recruit families; BEP developed an all-remote natural history study with periodic visits scheduled over a 2-year period. Inclusion was a diagnosis of SLC13A5 citrate transporter disorder, with confirmatory genetic testing. The caregiver’s clinical global and seizure specific impressions, seizure frequency, duration, and semiology as well as a seizure diary and current anti-seizure medications were studied. The data was collected by BEP or RMS and stored on Stanford Redcap.

Results: Age range at time of visit was 6 months to 30 years, average 12.6 years, with 8 males and 8 females. Nine of sixteen patient caregiver’s global impression were stable for the preceding 3 months though improvement was noted in 5/16 and worsening in 2/16, See Table1. Seizure frequency was unchanged in 8/16 or improved in 5/16 and 11/16 had stable seizure duration, Table 1. The seizure burden in 13 patients over the three months prior to the initial visit varied widely with 6 patients experiencing no seizures and one patient experiencing approximately 355 seizures.  All reported seizures had a motor component, focal motor with and without secondary generalization, and tonic clonic seizures. Though one patient at 20 years of age has been off medication and seizure free since 4 years of age, the other five seizure free patients remained on a mixture of anti-seizure medications. On average, patients were on 3 daily anti-seizure medications see Table 2 for a full list. Valproic acid was being taken by 10/13 patients with 4 patients’ seizure free and 7/10 caregivers reporting valproic acid was helpful or very helpful for seizure control.

Conclusions: Caregiver global impression and seizure burden was mostly stable with some improvement or worsening in a few patients. Most, 12/13 patients remain on medication and approximately half have ongoing and frequent seizures in the face of multiple anti-seizure medications. Valproic acid was the most used and caregivers felt it was helpful. While rare, patients with SLC13A5 can outgrow their epilepsy. Interestingly, the seizure free patient has two younger siblings 13.6 and 18 year of age (with the same SLC13A5 variants) on multiple anti-seizure medications and having frequent seizures, making it difficult to attribute this good outcome to a milder SLC13A5 mutations. Improved seizure control on fewer anti-seizure medications remains an unmet need in most older patients with SLC13A5 citrate transporter disorder.

Funding: TESS Research Foundation