A simple blood test expedites the diagnosis of glucose transporter type 1 deficiency syndrome

Domitille Gras, Christelle Cousin, Caroline Kappeler, Cheuk-Wing Fung, Stéphane Auvin, Nouha Essid, Brian Hy Chung, Lydie Da Costa, Elodie Hainque, Marie-Pierre Luton, Vincent Petit, Sandrine Vuillaumier-Barrot, Odile Boespflug-Tanguy, Emmanuel Roze, Fanny Mochel, Domitille Gras, Christelle Cousin, Caroline Kappeler, Cheuk-Wing Fung, Stéphane Auvin, Nouha Essid, Brian Hy Chung, Lydie Da Costa, Elodie Hainque, Marie-Pierre Luton, Vincent Petit, Sandrine Vuillaumier-Barrot, Odile Boespflug-Tanguy, Emmanuel Roze, Fanny Mochel

Abstract

Glucose transporter type 1 (GLUT1) deficiency syndrome (GLUT1-DS) leads to a wide range of neurological symptoms. Ketogenic diets are very efficient to control epilepsy and movement disorders. We tested a novel simple and rapid blood test in 30 patients with GLUT1-DS with predominant movement disorders, 18 patients with movement disorders attributed to other genetic defects, and 346 healthy controls. We detected significantly reduced GLUT1 expression only on red blood cells from patients with GLUT1-DS (23 patients; 78%), including patients with inconclusive genetic analysis. This test opens perspectives for the screening of GLUT1-DS in children and adults with cognitive impairment, movement disorder, or epilepsy. Ann Neurol 2017;82:133-138.

© 2017 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.

Figures

Figure 1
Figure 1
(A) Repeatability: GLUT1‐DS patient P26 was analyzed 12 times along with a healthy control, in the same experiment. Standard deviations are shown, which translate into CVs below 2.5%, pointing out the test's high repeatability. (B,C,D) Reproducibility: GLUT1‐DS patient P26 was analyzed along with 5 healthy control samples. Experiment was repeated three times (3 days) by three operators in two distinct labs. Mean GLUT1 expression and standard deviations are plotted for each sample and each operator. Results were highly correlated between operators (all R2 > 0.98). No significant difference was found between days, operators, nor labs; results were highly reproducible (Levene's test; all p values, > 0.93). CVs = coefficients of variation; GLUT1 = glucose transporter type 1; GLUT1‐DS = glucose transporter type 1 deficiency syndrome.
Figure 2
Figure 2
GLUT1 expression levels on RBC quantified by flow cytometry, expressed as % of mean of healthy controls. Twenty‐three GLUT1‐DS patients, of 30 (black dots), clustered in a specific group, clearly distinct from 18 patients with other gene‐related movement disorders (white squares) and 346 healthy controls—the black curve represents the distribution fitting of a normal law to the series of data (healthy controls only). GLUT1 = glucose transporter type 1; GLUT1‐DS = glucose transporter type 1 deficiency syndrome; RBC = red blood cells; SD = standard deviation.

References

    1. Leen WG, Klepper J, Verbeek MM, et al. Glucose transporter‐1 deficiency syndrome: the expanding clinical and genetic spectrum of a treatable disorder. Brain 2010;133:655–670.
    1. 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.
    1. Klepper J, Leiendecker B. Glut1 deficiency syndrome and novel ketogenic diets. J Child Neurol 2013;28:1045–1048.
    1. Mochel F, Hainque E, Gras D, et al. Triheptanoin dramatically reduces paroxysmal motor disorder in patients with GLUT1 deficiency. J Neurol Neurosurg Psychiatry 2016;87:550–553.
    1. Tang M, Gao G, Rueda CB, et al. Brain microvasculature defects and Glut1 deficiency syndrome averted by early repletion of the glucose transporter‐1 protein. Nat Commun 2017;8:14152.
    1. Gras D, Roze E, Caillet S, et al. GLUT1 deficiency syndrome: an update. Rev Neurol (Paris) 2014;170:91–99.
    1. Yang H, Wang D, Engelstad K, et al. Glut1 deficiency syndrome and erythrocyte glucose uptake assay. Ann Neurol 2011;70:996–1005.
    1. Klepper J. GLUT1 deficiency syndrome in clinical practice. Epilepsy Res 2012;100:272–277.
    1. Chordas C. Post‐dural puncture headache and other complications after lumbar puncture. J Pediatr Oncol Nurs 2001;18:244–259.
    1. Verrotti A, D’Egidio C, Agostinelli S, Gobbi G. Glut1 deficiency: when to suspect and how to diagnose? Eur J Paediatr Neurol 2012;16:3–9.
    1. Montel‐Hagen A, Blanc L, Boyer‐Clavel M, et al. The Glut1 and Glut4 glucose transporters are differentially expressed during perinatal and postnatal erythropoiesis. Blood 2008;112:4729–4738.
    1. Cretenet G, Clerc I, Matias M, et al. Cell surface Glut1 levels distinguish human CD4 and CD8 T lymphocyte subsets with distinct effector functions. Sci Rep 2016;6:24129.
    1. Wang D, Pascual JM, Yang H, et al. Glut‐1 deficiency syndrome: clinical, genetic, and therapeutic aspects. Ann Neurol 2005;57:111–118.
    1. Weber YG, Storch A, Wuttke TV, et al. GLUT1 mutations are a cause of paroxysmal exertion‐induced dyskinesias and induce hemolytic anemia by a cation leak. J Clin Invest 2008;118:2157–2168.

Source: PubMed

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