Abstract Introduction Sleep and metabolism interact bidirectionally, yet the metabolic requirements of sleep remain understudied. Pediatric genetic metabolic disorders provide a unique window into how metabolism shapes sleep physiology during development. GLUT1 deficiency syndrome (G1D) is a rare monogenic disease characterized by reduced cerebral glucose levels, with symptoms including epilepsy, movement disorders and intellectual disability. A third of G1D patients reported sleep disturbances in a recent Natural History study. Thus, our aim is to characterize sleep structure in a G1D cohort. Leveraging an age-matched normative populations, we identified lighter and fragmented sleep in G1D. Methods In a cohort of genetically confirmed G1D population (n=45) we preliminary analyzed overnight EEG (n=10). Standard sleep-stage scoring (AASM criteria) was performed, quantifying total sleep time, wake after sleep onset, REM latency, Sleep Fragmentation Index, REM interruptions, and stage distribution. A normative population (n= 267) was selected from Retrospective Analysis of Sleep in Pediatric, Cleveland Children’s Sleep and Health Study and Queensland Children’s Hospital data. For each sleep descriptor, normative data was fitted with a linear mixed effect model (MATLAB) using the interaction of age and sex. Chi-square analysis (two-sided, Fisher’s method) was used to compute group-level alignment between G1D and the normative population. Relative likelihood (proxy of adherence to normative population for a single patient) was computed for each sleep metric. Results Compared to age- and sex-matched normative population, the G1D cohort (n=10) showed significantly higher N1 stage percentage (χ2(20)=39.85,p=8∙10-4), Sleep Fragmentation Index (χ2(20)=91.97,p=1∙10-12), and REM interruptions (χ2(20)=113.54,p=1∙10-17). Other sleep metrics were not statistically different. Across all descriptors, regardless of significance, G1D population showed a wide spectrum of sleep patterns, ranging from mild deviation to not-normative. Geometric mean of the relative likelihood across patients (normative=1; atypical=0) averaged 0.26±0.16 (between 1.5 and 2.5 standard deviation from the normative mean), indicative of a moderate atypical sleep architecture at the group-level. Conclusion G1D cohort showed atypical sleep profile, with fragmented architecture and increased N1-sleep. In this first-of-its-kind sleep study in this pediatric genetic metabolic disorder, findings indicate that cerebral glucose hypometabolism is sufficient to disrupt sleep macroarchitecture, highlighting metabolism’s critical role in shaping sleep architecture during neurodevelopment. Support (if any)
Quaranta et al. (Fri,) studied this question.