Sleep Abnormalities in SLC13A5 Citrate Transporter Disorder
Abstract number :
1.235
Submission category :
2. Translational Research / 2D. Models
Year :
2024
Submission ID :
945
Source :
www.aesnet.org
Presentation date :
12/7/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Raegan Adams, BS – University of Texas Southwestern Medical Center
Can Ozlu, MD – University of Texas Southwestern Medical Center
Lauren Bailey, MS – University of Texas Southwestern Medical Center
Rayann Solidum, MS – Stanford Medicine
Sydney Cooper, MS – University of Texas Southwestern Medical Center
Carrie Best, MPH – Rhode Island Hospital
Jennifer Elacio, MS – Rhode Island Hospital
Tanya Brown, PhD – TESS Research Foundation
Kim Nye, AB – TESS Research Foundation
Judy Liu, MD, PhD – Rhode Island Hospital
Brenda Porter, MD, PhD – Stanford Medicine
Rachel Bailey, PhD – University of Texas Southwestern Medical Center
Rationale: SLC13A5 Citrate Transporter Disorder is a rare pediatric neurodevelopmental disorder. Patients have epilepsy, developmental disability, and impaired mobility with varying severity. While sleeping disorders are common in children with neurodevelopmental disorders, sleep abnormalities have not been reported in SLC13A5 patients. Here, we assessed sleep in both human patients and a mouse model of SLC13A5 Citrate Transporter Disorder.
Methods: Patients were recruited via the TESS research foundation, and all were genetically confirmed for SLC13A5 Citrate Transporter Disorder. The Sleep Disturbances Scale for Children (SDSC) was completed by the patient's caregivers at baseline, 6 month, and 12-month timepoints. This cohort included 26 patients.
Slc13a5 KO mice at baseline have increased neuronal excitability and metabolic perturbations, similar to those reported in patients. Three-month-old KO and WT littermates were surgically implanted with wireless telemetry probes. Approximately ten days following surgery, motor activity and sleep states were assessed using EEG and EMG signals over 2, 60-hour recording sessions. Neuroscore was used to analyze data. Sleep structure was divided into active wake, quiet wake, slow wave sleep, and paradoxical sleep using a combination of movement, muscle tone and EEG signals.
Results: Human: At baseline, 69.2% of patients (18/26) had SDSC scores in the clinically significant range across the duration of study. Surprisingly, less than 30% of patients are currently taking sleep aids. Sleep Wake Transition disorders (8/26) and Disorders of Initiating and Maintaining Sleep (5/26) had the highest percentages of affected patients, while Disorders of Excessive Somnolence (1/26) and Sleep Hyperhydrosis (0/26) had the lowest positive scores. Sleeping disorders were heterogenous in patients with a high penetrance and stability in symptoms over time.
Mouse: During the light cycle, when nocturnal mice typically sleep, Slc13a5 KO mice had significantly higher activity levels than WT littermates, while activity was similar amongst genotypes in the dark cycle, suggesting that Slc13a5 KO mice slept less per 24-hour cycle. When sleep structure was assessed, KO mice spent about 50% less time in paradoxical sleep than WT mice, while similar time was spent in slow wave sleep and wake stages. Analysis of EEG powerbands showed that KO mice have significantly decreased band power during the light cycle and during paradoxical and slow wave sleep stages. Further, during paradoxical sleep, theta and alpha band power were significantly lower in KO mice compared to WT mice.
Conclusions: Our results demonstrate a significant component of sleep disturbances in SLC13A5 patients and mice. Further investigation into the etiology of sleep disturbances and impact on overall function is warranted.
Funding: This work was supported by the TESS Foundation.
Translational Research