Sleep Abnormalities in SLC13A5 Citrate Transporter Disorder
Raegan M Adams1, Can Ozlu2, Lauren E Bailey1
1Center for Alzheimer's and Neurodegenerative Diseases, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Insights
Sleep disturbances are common in children with SLC13A5 Citrate Transporter Disorder, impacting patients and a mouse model. These findings suggest a need for better diagnosis and care for sleep issues in this rare neurodevelopmental disorder.
Area of Science:
- Neuroscience
- Pediatric Neurology
- Sleep Medicine
Background:
- SLC13A5 Citrate Transporter Disorder is a rare pediatric neurodevelopmental disorder characterized by epilepsy, developmental disability, and impaired mobility.
- Sleep disorders are frequently observed in children with neurodevelopmental disorders, but have not been previously reported in SLC13A5 patients.
Purpose of the Study:
- To investigate the prevalence and characteristics of sleep disturbances in patients with SLC13A5 Citrate Transporter Disorder.
- To assess sleep abnormalities in a transgenic mouse model of SLC13A5 deficiency.
Main Methods:
- Caregiver-reported surveys using the Sleep Disturbance Scale for Children were administered to 26 patients over one year.
- Sleep and wake activities in SLC13A5 knock-out (KO) mice were monitored using wireless telemetry and EEG recordings.
Main Results:
- Patients reported a high burden of clinically significant, heterogeneous sleep disturbances that remained stable over time.
- SLC13A5 KO mice exhibited significant sleep alterations, including increased activity and decreased paradoxical sleep during typical sleep periods, indicating disrupted sleep architecture.
Conclusions:
- The study demonstrates a significant presence of sleep disturbances in both SLC13A5 patients and the mouse model.
- These findings highlight a potential gap in clinical care for SLC13A5 Citrate Transporter Disorder and warrant further investigation into sleep dysfunction.
Background:
SLC13A5 Citrate Transporter Disorder is a rare pediatric neurodevelopmental disorder. Patients have epilepsy, developmental disability, and impaired mobility. While sleep disorders are common in children with neurodevelopmental disorders, sleep abnormalities have not been reported in SLC13A5 patients.
Methods:
Here, we assessed sleep disturbances in patients through caregiver reported surveys and in a transgenic mouse model of SLC13A5 deficiency. A total of 26 patients were evaluated with the Sleep Disturbance Scale for Children three times over a one-year span. Sleep and wake activities were assessed in the SLC13A5 knock-out (KO) mice using wireless telemetry devices.
Results:
A high burden of clinically significant sleep disturbances were reported in the patients, with heterogeneous symptoms that remained stable across time. While sleep disturbances were common, less than 30% of patients were prescribed medications for sleep. Comparatively, in SLC13A5 KO mice using EEG recordings, significant alterations were found during light cycles, when rodents typically sleep. During the sleep period, SLC13A5 mice had increased activity, decreased paradoxical sleep, and changes in absolute power spectral density, indicating altered sleep architecture in the mouse model.
Conclusions:
Our results demonstrate a significant component of sleep disturbances in SLC13A5 patients and mice, highlighting a potential gap in patient care. Further investigation of sleep dysfunction and the underlying etiologies of sleep disturbances in SLC13A5 citrate transporter disorder is warranted.
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