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.

Keywords

glucose transporter type-1 deficiency syndrome - familial Glut1 DS - sleep disorder - daytime somnolence - seizure - paroxysmal exercise-induced dyskinesia

Ethics Approval

This research was approved by the Committee on Human Rights related to Research involving Human Subjects, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand (ID number: MURA2020/308). The parents and patients provide written informed consent for the publication of all information in this case report.

Note

The work was conducted at Ramathibodi hospital, Mahidol University, Bangkok, Thailand.

Publikationsverlauf

Eingereicht: 17. Mai 2021

Angenommen: 12. August 2021

Artikel online veröffentlicht:
21. Oktober 2021

• References

• 1 Brockmann K. The expanding phenotype of GLUT1-deficiency syndrome. Brain Dev 2009; 31 (07) 545-552
• 2 De Giorgis V, Veggiotti P. GLUT1 deficiency syndrome 2013: current state of the art. Seizure 2013; 22 (10) 803-811
• 3 Gras D, Roze E, Caillet S. et al. GLUT1 deficiency syndrome: an update. Rev Neurol (Paris) 2014; 170 (02) 91-99
• 4 De Giorgis V, Varesio C, Baldassari C. et al. Atypical manifestations in Glut1 deficiency syndrome. J Child Neurol 2016; 31 (09) 1174-1180
• 5 Wang D, Pascual JM, De Vivo D. Glucose transporter type 1 deficiency syndrome. In: Adam MP, Ardinger HH, Pagon RA. et al., eds GeneReviews. Seattle, WA: University of Washington, Seattle; 2002
• 6 Tacik P, Loens S, Schrader C, Gayde-Stephan S, Biskup S, Dressler D. Severe familial paroxysmal exercise-induced dyskinesia. J Neurol 2014; 261 (10) 2009-2015
• 7 De Giorgis V, Masnada S, Varesio C. et al. Overall cognitive profiles in patients with GLUT1 deficiency syndrome. Brain Behav 2019; 9 (03) e01224
• 8 Klepper J, Diefenbach S, Kohlschütter A, Voit T. Effects of the ketogenic diet in the glucose transporter 1 deficiency syndrome. Prostaglandins Leukot Essent Fatty Acids 2004; 70 (03) 321-327
• 9 Ramm-Pettersen A, Nakken KO, Haavardsholm KC, Selmer KK. GLUT1-deficiency syndrome: report of a four-generation Norwegian family with a mild phenotype. Epilepsy Behav 2017; 70 (pt A): 1-4
• 10 Klepper J, Akman C, Armeno M. et al. Glut1 deficiency syndrome (Glut1DS): State of the art in 2020 and recommendations of the international Glut1DS study group. Epilepsia Open 2020; 5 (03) 354-365
• 11 Hully M, Vuillaumier-Barrot S, Le Bizec C. et al. From splitting GLUT1 deficiency syndromes to overlapping phenotypes. Eur J Med Genet 2015; 58 (09) 443-454
• 12 Wang D, Pascual JM, Yang H. et al. Glut-1 deficiency syndrome: clinical, genetic, and therapeutic aspects. Ann Neurol 2005; 57 (01) 111-118
• 13 Amalou S, Gras D, Ilea A. et al. Use of modified Atkins diet in glucose transporter type 1 deficiency syndrome. Dev Med Child Neurol 2016; 58 (11) 1193-1199
• 14 Musumeci O, Ferlazzo E, Rodolico C. et al. A family with a complex phenotype caused by two different rare metabolic disorders: GLUT1 and very-long-chain fatty acid dehydrogenase (VLCAD) deficiencies. Front Neurol 2020; 11: 514
• 15 Takahashi S, Matsufuji M, Yonee C, Tsuru H, Sano N, Oguni H. Somatic mosaicism for a SLC2A1 mutation: implications for genetic counseling for GLUT1 deficiency syndrome. Clin Genet 2017; 91 (06) 932-933