GLUT-1 DEFICIENCY: FROM PATHOPHYSILOGY AND GENETICS TO ABROAD CLINICAL SPECTRUM
The classical GLUT-1 deficiency syndrome (GLUT-1 DS, De Vivo disease) was described over 2 decades ago as a metabolic encephalopathy characterized by developmental delay, secondary microcephaly paroxysmal neurological symptoms (epilepsy) and movement disorders. The biochemical parameters of this disease, used in diagnosis, are low levels of glucose in the cerebrospinal fluid, normal level of glucose in the blood and consequent low ratio of cerebrospinal fluid vs. blood glucose levels (<40-45%). So far, more than 200 cases of the classical GLUT-1 DS have been described in the literature. Genetic research demonstrated that this disease is caused by mutations in SLC2A1 gene coding for GLUT-1, a transporter of glucose across the blood brain barrier. Over the last few years the clinical spectrum of GLUT-1 deficiencywas expanded to include other rare diseases such as paroxysmal exertional dyskinesia and early-onset absence epilepsy, but also some more common diseases such as idiopathic generalised epilepsy (1-2%). GLUT-1 deficiency is an important pathophysiological basis of these diseases as early diagnosis (aided by DNA mutation testing) and treatment (ketogenic diet) could lead to improved disease outcomes.
De Giorgis V, Veggiotti P. GLUT1 deficincy syndrome 2013: Current state of the art.Seizure. 2013; 22(10): 803-11.
Pearson ST, Akman C, Hinton JV, Engelstad K, De Vivo CD. Phenotypic Spectrum of Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS). Curr Neurol Neurosci Rep. 2013; 13(4): 342-51.
Pascual JM, Wang D, Lecumberri B, et al. GLUT1 deficiency and other glucose transporter diseases.Eur J Endocrinol.2004; 150(5): 627-33.
Rotdtein M, Engelstad K, Yang H, et al. Glut1 Deficiency: Inheritance Pattern Determined by Haploinsufficiency. Ann Neurol. 2010; 68(6): 955-8.
Seidner G, Alvarez MG, Yeh JI, et al. GLUT-1 dificiency syndrome caused by haploinsufficiency of the blood-brain barrier hexose carrier. Nat Genet. 1998; 18(2): 188-91.
Pascual JM, Ronen GM. Glucose Transporter Type I Deficiency (G1D) at 25 (1990-2015): Presumptions, facts, and the lives of persons with this rare disease. Pediatr Neurol. 2015; 53(5):379-93.
Melnikova AM, Korff CM. Clinical variability of GLUT1DS. Pediatr Neurol Briefs. 2015; 29(2):14.
Wang D, Pascual MJ, Yang H, et al. A mouse model for Glut-1 haploinsufficiency. Hum Mol Genet. 2006; 15(7):1169-79.
Strzelczyk A, Bürk K, Oertel WH. Treatment of paroxysmal dyskinesias. Expert Opin Pharmacother. 2011; 12(1): 63–72.
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(Pt7)): 1831-44.
Weber GY, Storch A, Wuttke VT, et al. GLUT1 mutations are a cause of paroxysmal exertion-induced dyskinesias and induce hemolytic anemia by a cation leak. J Clin Invest. 2008; 118(6): 2157-68.
Schneider AS, Paisan-Ruiz C, Garcia-Gorostiaga I, et al. GLUT1 Gene Mutations Cause Sporadic Paroxysmal Exercise-Induced Dyskinesias. Movement Disorders. 2009; 24(11): 1684–8.
Erro R, Sheerin UM, Bhatia PK. Paroxysmal dyskinesias revisited: A review of 500 genetically proven cases and a new classification. Mov Disord. 2014; 29(9): 1108-16.
Berkovic SF. Genetics of epilepsy in clinical practice. Epilepsy Curr. 2015; 15(4): 192–6.
Suls A, Mullen SA, Weber YG,et al. Early-onset absence epilepsy caused by mutations in the glucose transporter GLUT1. Ann Neurol. 2009; 66(3):415–9.
Arsov T, Mullen AS, Damiano AJ, et al. Early onset absence epilepsy: 1 in 10 cases is caused by GLUT1 deficiency. Epilepsia. 2012; 53(12):204–7.
Arsov T, Mullen AS, Rogers S, et al. Glucose transporter 1 deficiency in the idiopathic generalized epilepsies. Ann Neurol. 2012; 72(5):807–15.
Lebon S, Suarez P, Alija S, et al. When should clinicians search for GLUT1 deficiency syndrome in childhood generalized epilepsies? Eur J Paediatr Neurol. 2015; 19(2): 170-5.
Anand G, Padeniya A, Hanrahan D, et al. Milder phenotypes of glucose transporter type 1 deficiency syndrome. Dev Med Chil Neurol. 2011; 53(7): 664–8.
Kass RHR, Winesett SP, Bessone SK, Turner Z, Kossoff EH. Use of dietary therapies amongst patients with GLUT1 deficiency syndrome. Seizure. 2016; 35: 83-7.
Fujii T, Ito Y, Takahashi S, et al. Outcome of ketogenic diets in GLUT1 deficiency syndrome in Japan: A nationwide survey. Brain Dev. 2016; http://dx.doi.org/10.1016/j.braindev.2016.01.002
Akman CI, Yu J, Alter A, Engelstad K, De Vivo CD. Diagnosing glucose transporter 1 deficiency at initial presentation facilitates early treatment. J Pediatric..2016; 171: 220-6.
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