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Clinical nutrition

Glucose transporter 1 deficiency syndrome: nutritional and growth pattern phenotypes at diagnosis



Glucose Transporter 1 Deficiency Syndrome (GLUT1-DS; OMIM #606777) is a rare disease caused by dominant mutations in SLC2A1 encoding GLUT1, which is a ubiquitous transporter of glucose across plasma membranes, particularly across the blood-brain barrier. Hypoglycorrhachia symptoms are the cornerstones of GLUT1-DS, but delayed growth has also been suggested. This led us to investigate, at diagnosis, the relationship between the glycemia/glycorrhachia ratio and the nutritional and growth pattern phenotype of 30 GLUT-DS patients.


An assessment was made of body weight (BW), body length/height (BL, BH) and body composition by anthropometry and DEXA, and the results put with BL and BW at birth, genetic target, glycemia, insulinemia, and glycorrhachia values.


At birth, 21% of patients had a BW below −1.645 z-score, whereas no patients had BL below the reference values. At diagnosis 23% of the patients had an impaired nutritional status, 19.2% and 3.8% being respectively underweight and overweight/obese; 10%, all under 10 years old, had BL/BH below −1.645 z-score, with no specific features related to body composition. Finally, there was no association between glycemia, glycorrhachia, and growth phenotype.


GLUT1-DS is associated with impaired BW but not BL intrauterine growth, with a slower than normal pattern of growth rather than growth failure. These data could be useful for the interpretation of any long-term effects of the ketogenic diet, e.g. nutritional and growth pattern decline.

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  1. De Giorgis V, Veggiotti P. GLUT1 deficiency syndrome 2013: current state of the art. Seizure. 2013;22:803–11.

    Article  Google Scholar 

  2. Uldry M, Thorens B. The SLC2 family of facilitated hexose and polyol transporters. Pflug Arch. 2004;447:480–9.

    Article  CAS  Google Scholar 

  3. Maher F, Vannucci SJ, Simpson IA. Glucose transporter proteins in brain. Faseb J. 1994;8:1003–11.

    Article  CAS  Google Scholar 

  4. Klepper J, Leiendecker B. GLUT1 deficiency syndrome-2007 update. Dev Med Child Neurol. 2007;49:707–16.

    Article  Google Scholar 

  5. Klepper J. GLUT1 deficiency syndrome in clinical practice. Epilepsy Res. 2012;100:272–7.

    Article  CAS  Google Scholar 

  6. Klepper J. Glucose transporter deficiency syndrome (GLUT1DS) and the ketogenic diet. Epilepsia. 2008;49 Suppl 8:46–9.

    Article  Google Scholar 

  7. Klepper J, Diefenbach S, Kohlschutter A, Voit T. Effects of the ketogenic diet in the glucose transporter 1 deficiency syndrome. Prostaglandins Leukot Ess Fat Acids. 2004;70:321–7.

    Article  CAS  Google Scholar 

  8. De Giorgis V, Masnada S, Varesio C, Chiappedi MA, Zanaboni M, Pasca L, et al. Overall cognitive profiles in patients with GLUT1 deficiency syndrome. Brain Behav. 2019;0:e01224.

    Article  Google Scholar 

  9. Phase 2 Study of Triheptanoin (UX007) for the Treatment of Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS). Identifier: NCT01993186. Accessed 21 Jan 2019.

  10. Nakagama Y, Isojima T, Mizuno Y, Takahashi N, Kitanaka S, Igarashi T. Growth hormone deficiency: a possible complication of glucose transporter 1 deficiency? Acta Paediatr. 2012;101:e259–62.

    Article  Google Scholar 

  11. Bertoli S, Neri IG, Trentani C, Ferraris C, De Amicis R, Battezzati A, et al. Short-term effects of ketogenic diet on anthropometric parameters, body fat distribution, and inflammatory cytokine production in GLUT1 deficiency syndrome. Nutrition. 2015;31:981–7.

    Article  CAS  Google Scholar 

  12. Tanner JM, Goldstein H, Whitehouse RH. Standards for children’s height at ages 2-9 years allowing for heights of parents. Arch Dis Child. 1970;45:755–62.

    Article  CAS  Google Scholar 

  13. Wechsler D. Wechsler preschool and primary scale of intelligence. 4th ed. San Antonio, TX: Psychological Corporation; 2012.

  14. Orsini A, Pezzuti L, Picone L. Wechsler intelligence scale for children. 4th ed Italian Edition. Firenze, IT: Giunti O.S.; 2012.

  15. Griffiths R. The abilities of young children. A comprehensive system of mental measure for the first eight years of life: courns Wood House. North Dean, High Wycombe: The Test Agency;; 1984.

    Google Scholar 

  16. Lohman TG, Roche AF, Martorell R. Anthropometric standardization reference manual. Champaign, IL: Human Kinetics Books; 1988.

  17. Centers for Disease Control and Prevention, National Center for Health Statistics. CDC Growth Charts. 2000.

  18. Addo OY, Himes JH. Reference curves for triceps and subscapular skinfold thicknesses in US children and adolescents. Am J Clin Nutr. 2010;91:635–42.

    Article  CAS  Google Scholar 

  19. Metter EJ, Talbot LA, Schrager M, Conwit R. Skeletal muscle strength as a predictor of all-cause mortality in healthy men. J Gerontol A Biol Sci Med Sci. 2002;57:B359–65.

    Article  Google Scholar 

  20. Frisancho AR. Anthropometric standards for the assessment of growth and nutritional status. Ann Arbor, MI: University of Michigan Press; 1990.

  21. Butte NF, Hopkinson JM, Wong WW, Smith EO, Ellis KJ. Body composition during the first 2 years of life: an updated reference. Pediatr Res. 2000;47:578–85.

    Article  CAS  Google Scholar 

  22. McCarthy HD, Cole TJ, Fry T, Jebb SA, Prentice AM. Body fat reference curves for children. Int J Obes (Lond). 2006;30:598–602.

    Article  CAS  Google Scholar 

  23. Kelly TL, Wilson KE, Heymsfield SB. Dual energy X-Ray absorptiometry body composition reference values from NHANES. PLoS One. 2009;4:e7038.

    Article  Google Scholar 

  24. Spadafranca A, Cappelletti C, Leone A, Vignati L, Battezzati A, Bedogni G, et al. Relationship between thyroid hormones, resting energy expenditure and cardiometabolic risk factors in euthyroid subjects. Clin Nutr. 2015;34:674–8.

    Article  CAS  Google Scholar 

  25. Gandhi K. Approach to hypoglycemia in infants and children. Transl Pediatr. 2017;6:408–20.

    Article  PubMed  PubMed Central  Google Scholar 

  26. World Health Organization. Definition, diagnosis and classification of diabetes mellitus and its complications. Report of a WHO consultation. Part 1: Diagnosis and classification of diabetes mellitus. 59pWHO/NCD/NCS/99.2. Geneva: World Health Organization; 1999.

  27. Sperling MA. Pediatric endocrinology. 4 ed. Philadelphia, PA: Saunders Elsevier; 2014.

  28. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–9.

    Article  CAS  Google Scholar 

  29. Shashaj B, Luciano R, Contoli B, Morino GS, Spreghini MR, Rustico C, et al. Reference ranges of HOMA-IR in normal-weight and obese young Caucasians. Acta Diabetol. 2016;53:251–60.

    Article  CAS  Google Scholar 

  30. Muniyappa R, Lee S, Chen H, Quon MJ. Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage. Am J Physiol Endocrinol Metab. 2008;294:E15–26.

    Article  CAS  Google Scholar 

  31. Larsen J, Johannesen KM, Ek J, Tang S, Marini C, Blichfeldt S, et al. The role of SLC2A1 mutations in myoclonic astatic epilepsy and absence epilepsy, and the estimated frequency of GLUT1 deficiency syndrome. Epilepsia. 2015;56:e203–8.

    Article  CAS  Google Scholar 

  32. Coman DJ, Sinclair KG, Burke CJ, Appleton DB, Pelekanos JT, O’Neil CM, et al. Seizures, ataxia, developmental delay and the general paediatrician: glucose transporter 1 deficiency syndrome. J Paediatr Child Health. 2006;42:263–7.

    Article  Google Scholar 

  33. Ellis KJ, Shypailo RJ, Pratt JA, Pond WG. Accuracy of dual-energy x-ray absorptiometry for body-composition measurements in children. Am J Clin Nutr. 1994;60:660–5.

    Article  CAS  Google Scholar 

  34. Goran MI, Driscoll P, Johnson R, Nagy TR, Hunter G. Cross-calibration of body-composition techniques against dual-energy X-ray absorptiometry in young children. Am J Clin Nutr. 1996;63:299–305.

    Article  CAS  Google Scholar 

  35. Leen WG, Klepper J, Verbeek MM, Leferink M, Hofste T, van Engelen BG, et al. Glucose transporter-1 deficiency syndrome: the expanding clinical and genetic spectrum of a treatable disorder. Brain. 2010;133:655–70. Mar

    Article  Google Scholar 

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We would like to thank the patients with GLUT1 deficiency syndrome, their families, and the “Italian Association GLUT1 ONLUS” for their participation in the study. We also thank Greta Gambacorta for her help in the data collection, and Adrian Wallwork and Barbara Carey for the English revision.


This study was supported by the International Center for the Assessment of Nutritional Status (ICANS) and by the Department of Pediatrics, V. Buzzi Children’s Hospital, University of Milan.

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Authors and Affiliations



Conceptualization, SB and CM. Methodology, SB and CM. Formal analysis, AL. Investigation, RD, CL, CF, AS and MG. Data management, SB, CM, SM and PV. Writing—original draft preparation, SB, CM, AL, RD and SM. Writing—review and editing, AT, PV, AB, VD, and GZ. Funding acquisition, SB, CM, PV, and GZ. All authors approved the final version.

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Correspondence to Simona Bertoli.

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Bertoli, S., Masnada, S., De Amicis, R. et al. Glucose transporter 1 deficiency syndrome: nutritional and growth pattern phenotypes at diagnosis. Eur J Clin Nutr 74, 1290–1298 (2020).

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