Glucose transporter deficiency syndrome type 1: a case report

The authors present a unique clinical observation of the case of a hereditary deficiency of a type 1 glucose transporter, also called de Vivo disease. The type 1 glucose transporter deficiency syndrome (OMIM: 606777, ORPHA: 71277) is an extremely rare genetic disease associated with mutations in the SCL2A gene encoding the transfer of glucose across the blood-brain barrier. The clinical case, given in the article, replenishes the piggy bank of genetically verified glucose transport disruption syndromes leading to the development of polymorphic neurological disorders. The syndrome is most often inherited by an autosomal dominant pathway, but rare cases of autosomal recessive transmission are known. About 500 clinical cases of the present syndrome are described, although, according to various authors, the number of clinically verified cases not confirmed by genetic verification is much higher. In addition to the given data of the clinical course of the disease, detailed results of the genetic interpretation of the hereditary syndrome are given, the modern method of pathogenetic therapy is considered – the ketogenic diet.

1. Darbinyan V.Zh. Epilepsy and paroxysmal states. Clinic, diagnosis, treatment. Moscow, 2016. 264 p. (In Russ.).

2. Amaral A.I. Effects of hypoglycemia on neuronal metabolism in the adult brain: role of alternative substrates to glucose. J Inherit Metab Dis 2013;36(4):621–34. DOI: 10.1007/s10545-012-9553-3.

3. Bergqvist A.G. Long-term monitoring of the ketogenic diet: Do’s and Don’ts. Epilepsy Res 2012;100(3):261–6. DOI:10.1016/j.eplepsyres.2011.05.020.

4. Braakman H.M.H., Engelen M., Nicolai J., Willemsen M.A.A.P. Stroke mimics add to the phenotypic spectrum of GLUT1 deficiency syndrome. J Neurol Neurosurg Psychiatry 2018;89(6):668–70. DOI: 10.1136/jnnp-2017-316861.

5. Cappuccio G., Pinelli M., Alagia M. et al. Biochemical phenotyping unravels novel metabolic abnormalities and potential biomarkers associated with treatment of GLUT1 deficiency with ketogenic diet. PLoS One 2017;12(9):e0184022. DOI: 10.1371/journal.pone.0184022.

6. Daci A., Bozalija A., Jashari F., Krasniqi S. Individualizing treatment approaches for epileptic patients with glucose transporter type1 (GLUT1) deficiency. Int J Mol Sci 2018;19(1). PII: E122. DOI: 10.3390/ijms19010122.

7. De Vivo D.C., Leary L., Wang D. Glucose transporter 1 deficiency syndrome and other glycolytic defects. J Child Neurol 2002;17(suppl 3):15–23.

8. Freeman J.M., Kossoff E.H., Hartman A.L. The ketogenic diet: one decade later. Pediatrics 2017;119(3):535–43. DOI:10.1542/peds.2006-2447.

9. Kossoff E.H., Cervenka M.C., Henry B.J. et al. A decade of the modified Atkins diet (2003–2013): Results, insights, and future directions. Epilepsy Behav 2013;29(3):437–42.

10. Kossoff E.H., Hartman A.L. Ketogenic diets: new advances for metabolism-based therapies. Curr Opin Neurol 2012;25(2):173–8. DOI: 10.1097/WCO.0b013e3283515e4a.

11. Leary L.D., Wang D., Nordli D.R. et al. Seizure characterization and electroen-cephalographic features in GLUT1 deficiency syndrome. Epilepsia 2003;44:701–7.

12. Leen W.G., Wevers R.A., Kamsteeg E.J. et al. Cerebrospinal fluid analysis in the workup of GLUT-1 deficiency syndrome: A systematic review. JAMA Neurol 2013;70:1440–4.

13. Levy R.G., Cooper P.N., Giri P. Ketogenic diet and other dietary treatments for epilepsy. Cochrane Database Syst Rev 2012;(3):CD001903. DOI: 10.1002/14651858.CD001903.pub2.

14. Lukyanova E.G., Sushko L.M., Ayvazyan S.O. et al. Glucose transporter type 1 deficiency syndrome (GLUT1) and using ketogenic diet in treatment of de vivo disease: a case reports. Electr J Biol 2017;13(4):330–7.

15. National Library of Medicine, U.S. Genetics home reference: your guide to understanding genetic conditions. GLUT1 deficiency syndrome. Available at: https://ghr.nlm.nih.gov/condition/glut1-deficiencysyndrome

16. Pearson T.S., Akman C., Hinton V.J. et al. Phenotypic spectrum of glucose transporter type 1 deficiency syndrome (Glut1 DS). Curr Neurol Neurosci Rep 2013;13(4):342. DOI: 10.1007/s11910013-0342-7.

17. Pearson T.S., Pons R., Engelstad K. et al. Paroxysmal eye-head movements in Glut1 deficiency syndrome. Neurology 2017;88(17):1666–73. DOI: 10.1212/WNL.0000000000003867.

18. Pons R., Collins A., Rotstein M. et al. The spectrum of movement disorders in GLUT1 deficiency. Mov Disord 2010;25(3):275–81. DOI: 10.1002/mds.22808.

19. Sushko L.M., Lukyanova E.G., Ayvazyan S.O. et al. The ketogenic diet in the treatment of pharmacoresistant epilepsy in children. Quantum Satis 2017;1(2):35–44.

20. Tang M., Gao G., Rueda C.B. et al. Brain microvasculature defects and Glut1 deficiency syndrome averted by early repletion of the glucose transporter-1 protein. Nat Commun 2017;8:14152. DOI: 10.1038/ncomms14152.

21. Turner Z., Kossoff E.H. The ketogenic and Atkins diets: recipes for seizure control. Pract Gastroenterol 2006;29(6):53–64.

22. Veggiotti P., de Giorgis V. Dietary treatments and new therapeutic perspective in GLUT1 deficiency syndrome. Curr Treat Options Neurol 2014;16(5):291. DOI: 10.1007/s11940-014-0291-8.

23. Wang D., Pascual J.M., de Vivo D. Glucose transporter type 1 deficiency syndrome. In: GeneReviews®. Eds.: Adam M.P., Ardinger H.H., Pagon R.A. et al. Seattle: University of Washington, Seattle, 1993–2018. Available at: http://www.ncbi.nlm.nih.gov/books/NBK1430/

24. Wang D., Pascual J.M., Yang H. et al. GLUT1 deficiency syndrome: clinical, genetic, and therapeutic aspects. Ann Neurol 2005;57(1):111–8. DOI: 10.1002/ana.20331.

25. Yang H., Wang D., Engelstad K. et al. GLUT1 deficiency syndrome and erythrocyte glucose uptake assay. Ann Neurol 2011;70(6):996–1005. DOI: 10.1002/ana.22640.

26. Zupec-Kania B., Werner R.R., Zupanc M.L. Clinical use of the ketogenic diet – the dietitan’s role. In: Epilepsy and the ketogenic diet. Eds.: Stafstrrom C.E., Rho J.M. Totowa: Humana Press, 2004. Pp. 63–81.