Sleep Disorder: An Overlooked Manifestation of Glucose Transporter Type-1 Deficiency Syndrome

Abstract

Glucose transporter type-1 deficiency syndrome (Glut1 DS) is a rare disorder with various manifestations. Early diagnosis is crucial because treatment with the ketogenic diet can lead to clinical improvement. Here, we report the cases of two siblings with Glut1 DS and one of them presented with sleep disorder which is a rare and atypical manifestation of Glut1 DS. Patient 1 was a 3.5-year-old boy who presented with paroxysmal loss of tone and weakness of the whole body with unresponsiveness after waking up. He also had excessive daytime sleepiness, insomnia, and restless sleep. His other clinical findings included focal seizures, paroxysmal exercise-induced dyskinesia (PED), ataxia, mild global developmental delay, and hyperactivity. Patient 2 was a 5.5-year-old boy who presented with drug-resistant focal epilepsy, global developmental delay, paroxysmal dystonia, and ataxia. A novel heterozygous nonsense variant of SLC2A1, c.1177G > T (p.Glu393*), classified as a pathogenic variant, was identified in both patients, but not in their parents' blood. After treatment with the modified Atkins diet, their neurological functions significantly improved. In conclusion, we reported two siblings with variable phenotypes of Glut1 DS with a novel nonsense mutation. Although sleep disorder and daytime somnolence were the nonclassical manifestations of Glut1 DS, the diagnostic evaluation of possible Glut1 DS in patients presented with daytime sleepiness, particularly in cases with the cooccurrence of seizures or movement disorders should be considered.

The effects of ketogenic dietary therapies on sleep: A scoping review

“…A total of 20 articles published between 2001 and 2022 were included: nine prospective studies divided between eight single‐centre (Ebus et al, 2014; Guzel et al, 2019; Hallböök, Köhler, et al, 2007; Hallböök, Lundgren, & Rosén, 2007; Li et al, 2023; Merlino et al, 2023; Wu et al, 2018; Zhu et al, 2016) and one multi‐centre (Miranda et al, 2011), eight retrospective studies, divided between three single‐centre (Nordli et al, 2001; Peng et al, 2019; Reyes et al, 2015) and five multi‐centre, one of which longitudinal study (Sofou et al, 2017) and four cross‐sectional (Alqahtani & Mahmoud, 2016; Caraballo et al, 2011; Frye et al, 2011; Ünalp et al, 2021), two case reports (Anurat et al, 2022; Melikishvili et al, 2022), one two‐arm open RCT (Kverneland et al, 2018). Of these 20 articles, only one study is related to migraine while 18 studies have epilepsy as a starting diagnosis and one study is related to autism spectrum disorder.…”

“…In the studies included, sleep improvement was almost never preceded by a systematic screening for sleep disorder at baseline, before the initiation of ketogenic dietary therapies. One study reported an improvement of sleep disorder after ketogenic dietary therapy in the case description of a patient with GLUT1 deficiency syndrome, who presented with sleep‐onset insomnia and restless sleep during the night, together with excessive daytime sleepiness (Anurat et al, 2022). The polysomnography at baseline and Multiple Sleep Latency Test findings showed a pathological periodic limb movement index and daytime sleepiness.…”

An integrated multi-omics analysis identifies novel regulators of circadian rhythm and sleep disruptions induced by changed photoperiod in Antarctica

“…Our study suggested that SLC2A1 might be an upstream regulator of SHISA8. SLC2A1 is a glucose transporter primarily located in the blood-brain barrier [40] , whose nonsense or missense mutations induced daytime sleepiness and insomnia [41,42] . Although a recent study in a small cohort suggested increased glutamine level in cerebrospinal uid of SLC2A1 de ciency patients [43] , whether SLC2A1 affects sleep-wake activity through the glutaminergic system or SHISA8 remains largely unexplored.…”

Sleep and circadian rhythm dysfunctions in movement disorders beyond Parkinson's disease and atypical parkinsonisms

“…A high frequency of insomnia has been observed in Sydenham's chorea. Additionally, sudden sleep episodes, insomnia, EDS, and paroxysmal loss of tone or weakness upon awakening have been reported in glucose transporter type 1 deficiency syndrome (GLUT1-DS), a rare metabolic encephalopathy linked to paroxysmal exerciseinduced dyskinesias [49,50].…”