Glucose Transporter 1 deficiency and associated conditions in children
https://doi.org/10.21508/1027-4065-2019-64-5-155-158
Abstract
The article reviews literature devoted to the glucose transporter type I deficiency syndrome (synonyms: GLUT1 deficiency syndrome, de Vivo disease), that is a genetically determined disease caused by pathogenic variants of the SLC2A1 gene. The insufficiency of this protein leads to the disruption of glucose delivery to the brain through the blood-brain barrier. Clinically, the syndrome is manifested by epileptic seizures (mainly as absences or myoclonic seizures), various motor disorders and psychomotor retardation starting from the early age.
Early diagnosis (including molecular genetic analysis of the SLC2A1 gene) enables us to start treatment and prevent progression of the symptoms, and to provide the family with genetic consultation on the prognosis and risks for the next generations. Ketogenic diet is an effective treatment option for this pathological condition, it can lead to a regression of the clinical manifestations, especially on the early stage.
About the Authors
R. G. GamirovaRussian Federation
Kazan
Z. Afawi
Israel
Tel-Aviv
R. R. Gamirova
Russian Federation
Kazan
E. A. Gorobets
Russian Federation
Kazan
V. F. Prusakov
Russian Federation
Kazan
S. Ya. Volgina
Russian Federation
Kazan
References
1. De Vivo D.C., Trifiletti R.R., Jacobson R.I., Ronen G.M., Behmand R.A., Harik S.I. Defective glucose transport across the blood-brain barrier as a cause of persistent hypoglycorrhachia, seizures, and developmental delay. New England J Med 1991; 325(10): 703–709. DOI: 10.1056/NEJM199109053251006
2. Suls A., Dedeken P., Goffin K., Van Esch H., Dupont P., Cassiman D. et al. Paroxysmal exercise-induced dyskinesia and epilepsy is due to mutations in SLC2A1, encoding the glucose transporter GLUT1. Brain 2008; 131(7): 1831–1844. DOI: 10.1093/brain/awn113
3. Weber Y.G., Storch A., Wuttke T.V., Brockmann K., Kempfle J., Maljevic S. et al. GLUT1 mutations are a cause of paroxysmal exertion-induced dyskinesias and induce hemolytic anemia by a cation leak. J Сlin Invest 2008; 118(6): 2157–2168. DOI: 10.1172/JCI34438
4. Striano P., Weber Y.G., Toliat M.R., Schubert J., Leu C., Chaimana R. et al. GLUT1 mutations are a rare cause of familial idiopathic generalized epilepsy. Neurology 2012; 78(8): 557–562. DOI: 10.1212/WNL.0b013e318247ff54
5. Suls A., Mullen S.A., Weber Y.G., Verhaert K., Ceulemans B., Guerrini R. et al. Early‐onset absence epilepsy caused by mutations in the glucose transporter GLUT1. Ann Neurol 2009; 66(3): 415–419. DOI: 10.1002/ana.21724
6. Weber Y.G., Kamm C., Suls A., Kempfle J., Kotschet K., Schüle R. et al. Paroxysmal choreoathetosis/spasticity (DYT9) is caused by a GLUT1 defect. Neurology 2011; 77(10): 959–964. DOI: 10.1212/WNL.0b013e31822e0479
7. Rotstein M., Doran J., Yang H., Ullner P.M., Engelstad K., De Vivo D.C. Glut1 deficiency and alternating hemiplegia of childhood. Neurology 2009; 73(23): 2042–2044. DOI: 10.1212/WNL.0b013e3181c55ebf
8. Becker F., Schubert J., Weckhuysen S., Suls A., Grüninger S., Korn-Merker E. et al. Do Glut1 (glucose transporter type 1) defects exist in epilepsy patients responding to a ketogenic diet? Epilepsy Res 2015; 114: 47–51. DOI: 10.1016/j.eplepsyres.2015.04.012
9. Peeraer A., Damiano J.A., Bellows S.T., Scheffer I.E., Berkovic S.F., Mullen S.A. et al. Evaluation of GLUT1 variation in non-acquired focal epilepsy. Epilepsy Res 2017; 133: 54–57. DOI: 10.1016/j.eplepsyres.2017.04.007
10. Leen W.G., Klepper J., Verbeek M.M., Leferink M., Hofste T., van Engelen B.G. et al. Glucose transporter-1 deficiency syndrome: the expanding clinical and genetic spectrum of a treatable disorder. Brain 2010; 133: 655–670. DOI: 10.1093/brain/awp336
11. Hildebrand M.S., Damiano J.A., Mullen S.A. Bellows S.T., Oliver K.L., Dahl H.H.M. et al. Glucose metabolism transporters and epilepsy: Only GLUT 1 has an established role. Epilepsia 2014; 55(2): e18–e21. DOI: 10.1111/epi.12519
12. Mullen S.A., Suls A., De Jonghe P., Berkovic S.F., Scheffer I.E. Absence epilepsies with widely variable onset are a key feature of familial GLUT1 deficiency. Neurology 2010; 75(5): 432–440. DOI: 10.1212/WNL.0b013e3181eb58b4
13. Liu Y.C., Lee J.W.A., Bellows S.T., Damiano J.A., Mullen S.A., Berkovic S.F. et al. Evaluation of non-coding variation in GLUT1 deficiency. Dev Med Child Neurol 2016; 58(12): 1295–1302. DOI: 10.1111/dmcn.13163
14. Rotstein M., Engelstad K., Yang H., Wang D., Levy B., Chung W.K. et al. Glut1 deficiency: inheritance pattern determined by haploinsufficiency. Ann Neurol 2010; 68(6): 955–958. DOI: 10.1002/ana.22088
15. Mullen S.A., Marini C., Suls A., Mei D., Della Giustina E., Buti D. et al. Glucose transporter 1 deficiency as a treatable cause of myoclonic astatic epilepsy. Arch Neurol 2011; 68(9): 1152–1155. DOI: 10.1001/archneurol.2011.102
16. Arsov T., Mullen S. A., Rogers S., Phillips A. M., Lawrence K.M., Damiano J.A. et al. Glucose transporter 1 deficiency in the idiopathic generalized epilepsies. Ann Neurol 2012; 72(5): 807–815. DOI: 10.1002/ana.23702
17. Arsov T., Mullen S.A., Damiano J.A., Lawrence K.M., Huh L.L., Nolan M. et al. Early onset absence epilepsy: 1 in 10 cases is caused by GLUT1 deficiency. Epilepsia 2012; 53(12): e204–e207. DOI: 10.1111/epi.12007
18. Chugani H.T., Phelps M.E. Maturational changes in cerebral function in infants determined by 18FDG positron emission tomography. Science 1986; 231(4740): 840–843. DOI: 10.1126/science.3945811
19. Muhle H., Helbig I., Frøslev T.G., Suls A., von Spiczak S., Klitten L.L. et al. The role of SLC2A1 in early onset and childhood absence epilepsies. Epilepsy Res 2013; 105(1–2): 229–233. DOI: 10.1016/j.eplepsyres.2012.11.004
20. Neal E.G., Chaffe H., Schwartz R.H., Lawson M.S., Edwards N., Fitzsimmons G., et al. The ketogenic diet for the treatment of childhood epilepsy: a randomized controlled trial. Lancet Neurol 2008; 7: 500–506. DOI: 10.1016/S1474-4422(08)70092-9
21. Neal E.G., Chaffe H., Schwartz R.H., Lawson M.S., Edwards N., Fitzsimmons G et al. A randomized trial of classical and medium-chain triglyceride ketogenic diets in the treatment of childhood epilepsy. Epilepsia 2009; 50: 1109–1117. DOI: 10.1111/j.1528-1167.2008.01870.x
22. Nei M., Ngo L., Sirven J.L., Sperling M.R. Ketogenic diet in adolescents and adults with epilepsy. Seizure 2014; 23(6): 439–442. DOI: 10.1016/j.seizure.2014.02.015
Review
For citations:
Gamirova R.G., Afawi Z., Gamirova R.R., Gorobets E.A., Prusakov V.F., Volgina S.Ya. Glucose Transporter 1 deficiency and associated conditions in children. Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics). 2019;64(5):155-158. (In Russ.) https://doi.org/10.21508/1027-4065-2019-64-5-155-158