SLC13A5 citrate transporter disorder epilepsy phenotype

The SLC13A5 gene encodes a sodium citrate co-transporter, with loss of function variants causing autosomal recessive developmental and epileptic encephalopathy 25, DEE25. DEE25 is an ultra-rare genetic disorder, known to cause neonatal onset epilepsy as well as later neurocognitive and motor impairments. Here, we characterize the epilepsy phenotype from 30 children and adults enrolled in a prospective natural history study, with frequent visits over 2 years. Our findings reveal that the highest seizure burden and number of ER visits occurred during the first decade of life, with decreased seizure burden and ER visits after 10 years of age. However, older patients remained on an average of 3 antiseizure medications, and some had breakthrough seizures, suggesting ongoing epilepsy risk. Many antiseizure medications were used across patients. Multiple antiseizure medications were felt to be of benefit by caregivers, with valproic acid having the highest utilization with 22 patients and 80 % of caregivers reporting it to be helpful or very helpful. Higher doses of valproic acid correlated with caregiver reported benefit. All DEE25 pediatric epilepsy quality of life module scores were low, consistent with poor quality of life, and stable across the two years, with cognitive impairment, executive functioning being lower than mood and behavior. Most EEGs were abnormal, but less than a third had frequent or abundant interictal epileptiform activity, suggesting that interictal epileptiform activity was not a primary driver of neurocognitive dysfunction.