Journal of Inherited Metabolic Disease

, Volume 34, Issue 2, pp 483–488

Dystonic tremor caused by mutation of the glucose transporter gene GLUT1

  • Anne Roubergue
  • Emmanuelle Apartis
  • Valérie Mesnage
  • Diane Doummar
  • Jean-Marc Trocello
  • Emmanuel Roze
  • Guillaume Taieb
  • Thierry Billette De Villemeur
  • Sandrine Vuillaumier-Barrot
  • Marie Vidailhet
  • Richard Levy
Original Article

Abstract

Glucose transporter 1 deficiency syndrome (GLUT1-DS) is due to heterozygous mutation of the glucose transporter type 1 gene (GLUT1/SLC2A1). GLUT1-DS is characterized by movement disorders, including paroxysmal exercise-induced dystonia (PED), as well as seizures, mental retardation and hypoglycorrhachia. Tremor was recently shown to be part of the phenotype, but its clinical and electrophysiological features have not yet been described in detail, and GLUT1 tremor reports are rare. We describe two patients, a young woman and her mother, who were referred to us for tremor. We also systematically review published cases of GLUT1-DS with tremor (14 cases, including ours), focusing on clinical features. In most cases (10/14), the tremor, which involved the limbs and voice, fulfilled clinical criteria for dystonic tremor (DT), occurring in body areas affected by dystonia. Tremor was the only permanent symptom in 2 cases. Recordings, reported here for the first time, showed an irregular 6- to 8.5-Hz tremor compatible with DT in our two patients. These findings show that tremor, and particularly DT, may be a presenting symptom of GLUT1-DS. Patients who present with dystonic tremor, with or without mental retardation, seizures, movement disorders and/or a family history, should therefore be screened for GLUT1-DS.

References

  1. Bourdain F, Apartis E, Trocello JM et al (2006) Clinical analysis in familial cortical myoclonic tremor allows differential diagnosis with essential tremor. Mov Disord 21(5):599–608PubMedCrossRefGoogle Scholar
  2. Brockmann K (2009) The expanding phenotype of GLUT1-deficiency syndrome. Brain Dev 31(7):545–552PubMedCrossRefGoogle Scholar
  3. De Vivo DC, Trifiletti RR, Jacobson RI et al (1991) Defective glucose transport across the blood-brain barrier as a cause of persistent hypoglycorrhachia, seizures, and developmental delay. N Engl J Med 325(10):703–709PubMedCrossRefGoogle Scholar
  4. Deuschl G, Bain P, Brin M (1998) Consensus statement of the movement disorder society on tremor. Ad Hoc scientific committee. Mov Disord 13(suppl 3):2–23PubMedGoogle Scholar
  5. Elble RJ (2003) Characteristics of physiologic tremor in young and elderly adults. Clin Neurophysiol 114(4):624–635PubMedCrossRefGoogle Scholar
  6. Fujii T, Ho YY, Wang D et al (2007) Three Japanese patients with glucose transporter type 1 deficiency syndrome. Brain Dev 29(2):92–97PubMedCrossRefGoogle Scholar
  7. Jedynak CP, Bonnet AM, Agid Y (1991) Tremor and idiopathic dystonia. Mov Disord 6(3):230–236PubMedCrossRefGoogle Scholar
  8. Leen WG, Klepper J, Verbeek MM et al (2010) Glucose transporter-1 deficiency syndrome: the expanding clinical and genetic spectrum of a treatable disorder. Brain 133(3):655–670PubMedCrossRefGoogle Scholar
  9. Levy B, Wang D, Ullner PM et al (2010) Uncovering microdeletions in patients with severe Glut-1 deficiency syndrome using SNP oligonucleotide microarray analysis. Mol Genet Metab 100(2):129–135PubMedCrossRefGoogle Scholar
  10. Margari L, Perniola T, Illiceto G et al (2000) Familial paroxysmal exercise-induced dyskinesia and benign epilepsy: a clinical and neurophysiological study of an uncommon disorder. Neurol Sci 21(3):165–172PubMedCrossRefGoogle Scholar
  11. Mullen SA, Suls A, De Jonghe P et al (2010) Absence epilepsies with widely variable onset are a key feature of familial GLUT1 deficiency. Neurology 75(5):432–440PubMedCrossRefGoogle Scholar
  12. Müller U (2009) The monogenic primary dystonias. Brain 132(8):2005–2025PubMedCrossRefGoogle Scholar
  13. Münchau A, Valente EM, Shahidi GA et al (2000) A new family with paroxysmal exercise induced dystonia and migraine: a clinical and genetic study. J Neurol Neurosurg Psychiatry 68(5):609–614PubMedCrossRefGoogle Scholar
  14. Pascual JM, Van Heertum RL, Wang D et al (2002) Imaging the metabolic footprint of Glut1 deficiency on the brain. Ann Neurol 52(4):458–464PubMedCrossRefGoogle Scholar
  15. Pérez-Dueñas B, Prior C, Ma Q et al (2009) Childhood chorea with cerebral hypotrophy: a treatable GLUT1 energy failure syndrome. Arch Neurol 66(11):1410–1414PubMedCrossRefGoogle Scholar
  16. Pons R, Collins A, Rotstein M et al (2010) The spectrum of movement disorders in Glut-1 deficiency. Mov Disord 25(3):275–281PubMedGoogle Scholar
  17. Schneider SA, Paisan-Ruiz C, Garcia-Gorostiaga I et al (2009) GLUT1 gene mutations cause sporadic paroxysmal exercise-induced dyskinesias. Mov Disord 24(11):1684–1688PubMedCrossRefGoogle Scholar
  18. Suls A, Dedeken P, Goffin K et al (2008) Paroxysmal exercise-induced dyskinesia and epilepsy is due to mutations in SLC2A1, encoding the glucose transporter GLUT1. Brain 131(7):1831–1844PubMedCrossRefGoogle Scholar
  19. Suls A, Mullen SA, Weber YG et al (2009) Early-Onset absence epilepsy caused by mutations in the glucose transporter GLUT1. Ann Neurol 66(3):415–419PubMedCrossRefGoogle Scholar
  20. Toro C, Pascual-Leone A, Deuschl G et al (1993) Cortical tremor: a common manifestation of cortical myoclonus. Neurology 43(11):2346–2353PubMedGoogle Scholar
  21. Veggiotti P, Teutonico F, Alfei E et al (2010) Glucose transporter type 1 deficiency: ketogenic diet in three patients with atypical phenotype. Brain Dev 32(5):404–408PubMedCrossRefGoogle Scholar
  22. Wang D, Pascual JM, DeVivo D (2002–2009) Glucose transporter type 1 deficiency syndrome. In GeneReviews : Reviews. Retrieved from http://www.ncbi.nlm.nih.gov/sites/GeneTests/ (September 24 2010)
  23. Weber YG, Storch A, Wuttke TV et al (2008) GLUT1 mutations are a cause of paroxysmal exertion-induced dyskinesias and induce hemolytic anemia by a cation leak. J Clin Invest 118(6):2157–2168PubMedGoogle Scholar
  24. Zorzi G, Castellotti B, Zibordi F et al (2008) Paroxysmal movement disorders in GLUT1 deficiency syndrome. Neurology 71(2):146–148PubMedCrossRefGoogle Scholar

Copyright information

© SSIEM and Springer 2011

Authors and Affiliations

  • Anne Roubergue
    • 1
    • 2
    • 11
  • Emmanuelle Apartis
    • 3
    • 4
  • Valérie Mesnage
    • 2
  • Diane Doummar
    • 1
  • Jean-Marc Trocello
    • 5
  • Emmanuel Roze
    • 6
    • 7
    • 8
  • Guillaume Taieb
    • 9
  • Thierry Billette De Villemeur
    • 1
  • Sandrine Vuillaumier-Barrot
    • 10
  • Marie Vidailhet
    • 4
    • 6
  • Richard Levy
    • 2
    • 4
  1. 1.AP-HP, Service de NeuropédiatrieHôpital TrousseauParisFrance
  2. 2.AP-HP, Service de NeurologieHôpital St AntoineParisFrance
  3. 3.AP-HP, Service de PhysiologieHôpital St AntoineParisFrance
  4. 4.Université Pierre et Marie Curie-Paris-6, CRICM /Inserm UMR_S975 /CNRS UMR 7225ParisFrance
  5. 5.AP-HP, Centre National de Référence de la Maladie de WilsonHôpital LariboisièreParisFrance
  6. 6.AP-HP, Fédération des Maladies du Système NerveuxHôpital Pitié-SalpêtrièreParisFrance
  7. 7.AP-HP, Centre d’Investigation Clinique 9503INSERMParisFrance
  8. 8.Université Pierre et Marie Curie-Paris-6 INSERM UMRS 952, CNRS UMR 7224ParisFrance
  9. 9.Service de NeurologieHôpital Gui de ChauliacMontpellierFrance
  10. 10.AP-HP, Service de Biochimie AHôpital Bichat-Claude BernardParisFrance
  11. 11.Service de NeurologieHôpital Saint-AntoineParis Cedex12France

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