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GLUT1 deficiency

Glucose transporter 1 (GLUT1) deficiency is characterized by reduced expression of functional GLUT1 transporter and a heterogeneous phenotypic spectrum that may include microcephaly; cognitive impairment; absence, atonic, generalized tonic-clonic and focal seizures; ataxia; and dyskinesias.^1,2,3,4 Hypoglyccorrhachia with low-normal CSF lactate is suggestive of GLUT1 deficiency, while SLC2A1 gene sequencing typically confirms the diagnosis.^5,6 The ketogenic diet may reduce symptoms considerably and is most effective when started early in the disease course.^2,7 Gene therapy and other treatments are being actively pursued.⁶

References

1. Seidner G, Alvarez MG, Yeh JI, et al. GLUT-1 Deficiency Syndrome Caused by Haploinsufficiency of the Blood-Brain Barrier Hexose Carrier. Nat Genet 1998;18:188–191.
2.  Koch H, Weber, YG. The glucose transporter type 1 (Glut1) syndromes. Epilepsy Behav 2019;91:90–93.
3. De Vivo DC, Trifiletti RR, Jacobson RI, et al.  Defective glucose transport across the blood-brain barrier as a cause of persistent hypoglycorrhachia, seizures, and developmental delay. N Engl J Med 1991;325:703–709.
4. Suls A, Dedeken P, Goffin K, et al. Paroxysmal exercise-induced dyskinesia and epilepsy is due to mutations in SLC2A1, encoding the glucose transporter GLUT1. Brain 2008;131:1831–1844.
5. Leen WG, Wevers RA, Kamsteeg EJ, et al. Cerebrospinal fluid analysis in the workup of GLUT1 deficiency syndrome: a systematic review. JAMA Neurol 2013;70:1440–1444.
6. Tang M, Park SH, De Vivo DC, Monani UR. Therapeutic strategies for glucose transporter 1 deficiency syndrome. Ann Clin Transl Neurol 2019:6:1923–1932.
7. Klepper J, Leiendecker B. Glut1 deficiency syndrome and novel ketogenic diets. J Child Neurol 2013;28:1045–1048.

Samuel Mackenzie, MD, PhD, Child Neurology Residency Program, C.S. Mott Children's Hospital, University of Michigan (Ann Arbor)

Dr. Mackenzie receives compensation from Everyday Health, Inc. for medical review. He has one medical device patent pending.