Case report| Volume 27, ISSUE 4, P311-317, June 2005

Clinical presentation, EEG studies, and novel mutations in two cases of GLUT1 deficiency syndrome in Japan


      We report the first two Japanese children diagnosed with glucose transporter type 1 (GLUT1) deficiency syndrome. Both boys had been treated under the initial diagnosis of epilepsy and were reinvestigated for previously unexplainable hypoglycorrhachia. Myoclonic seizures developed at 4 months of age in Patient #1 (7 years old), and at 2 months of age in Patient #2 (11 years old), followed by cerebellar ataxia, spastic diplegia, and mental retardation. Both patients had hypoglycorrhachia, and the symptoms were more severe in the latter. CSF and serum glucose levels determined simultaneously showed a CSF/serum glucose ratio of below 0.4 in both patients. In mildly affected Patient #1, the postprandial waking EEG showed improvement in the background activity, as compared to that recorded after overnight fasting, while no significant changes were observed in severely affected Patient #2. In both patients, the functional GLUT1 defect was confirmed by 3-O-methyl-d-glucose uptake into erythrocytes. Molecular analyses identified heterozygous novel mutations in both patients, within exons 6 and 2 of the GLUT1 gene, respectively. The ketogenic diet was refused in Patient #1, but started in Patient #2 with significant clinical benefit. Fasting CSF analysis and pre-/postprandial EEG changes in children with epileptic seizures and unexplainable neurological deterioration help in diagnosing this potentially treatable disorder.


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        • Clarke D.D.
        • Sokoloff L.
        Circulation and energy metabolism of the brain. Substrates of cerebral metabolism.
        in: Siegel G.J. Agranoff B.W. Albers R.W. Molinoff P.B. Basic neurochemistry: molecular, cellular and medical aspects. 5th ed. Raven Press, New York1994: 666-671
        • Broman J.
        • Hassel E.
        • Rinvik E.
        • Ottersen O.P.
        Biochemistry and anatomy of transmitter glutamate.
        in: Ottersen O.P. Storm-Mathisen J. Handbook of chemical neuroanatomy. Glutamate. vol. 18. Elsevier, Amsterdam2000: 1-44
        • De Vivo D.C.
        • Trifiletti R.R.
        • Jacobson R.I.
        • Ronen G.M.
        • Behmand R.A.
        • Harik S.I.
        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
        • Klepper J.
        • Voit T.
        Facilitated glucose transporter protein type 1 (GLUT1) deficiency syndrome: impaired glucose transport into brain—a review.
        Eur J Pediatr. 2002; 161: 295-304
        • von Moers A.
        • Brockmann K.
        • Wang D.
        • Korenke C.G.
        • Huppke P.
        • De Vivo D.C.
        • et al.
        EEG features of glut-1 deficiency syndrome.
        Epilepsia. 2002; 43: 941-945
        • Pascual J.M.
        • Wang D.
        • Lecumberri B.
        • Yang H.
        • Mao X.
        • Yang R.
        • et al.
        GLUT1 deficiency and other glucose transporter diseases.
        Eur J Endocrinol. 2004; 150: 627-633
        • Klepper J.
        • Wang D.
        • Fischbarg J.
        • Vera J.C.
        • Jarjour I.T.
        • O'Driscoll K.
        • et al.
        Defective glucose transport across brain tissue barriers: a newly recognized neurological syndrome.
        Neurochem Res. 1999; 24: 587-594
        • Tao T.
        • Tanizawa Y.
        • Matsutani A.
        • Matsubara A.
        • Kaneko T.
        • Kaku K.
        HepG2/ erythrocyte glucose transporter (GLUT1) gene in NIDDM: a population association study and molecular scanning in Japanese subjects.
        Diabetologia. 1995; 38: 942-947
        • Orita M.
        • Suzuki Y.
        • Sekiya T.
        • Hayashi K.
        Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction.
        Genomics. 1989; 5: 874-879
        • Klepper J.
        • Willemsen M.
        • Verrips A.
        • Guertsen E.
        • Herrmann R.
        • Kutzick C.
        • et al.
        Autosomal dominant transmission of GLUT1 deficiency.
        Hum Mol Genet. 2001; 10: 63-68
        • Seidner G.
        • Alvarez M.G.
        • Yeh J.I.
        • O'Driscoll K.R.
        • Klepper J.
        • Stump T.S.
        • et al.
        GLUT-1 deficiency syndrome caused by haploinsufficiency of the blood–brain barrier hexose carrier.
        Nat Genet. 1998; 18: 188-191
        • Brockmann K.
        • Wang D.
        • Korenke C.G.
        • von Moers A.
        • Ho Y.Y.
        • Pascual J.M.
        • et al.
        Autosomal dominant glut-1 deficiency syndrome and familial epilepsy.
        Ann Neurol. 2001; 50: 476-485
        • Boles R.G.
        • Seashore M.R.
        • Mitchell W.G.
        • Kollros P.R.
        • Mofidi S.
        • Novotny E.J.
        Glucose transporter type 1 deficiency: a study of two cases with video-EEG.
        Eur J Pediatr. 1999; 158: 978-983
        • Gordon N.
        • Newton R.W.
        Glucose transporter type1 (GLUT-1) deficiency.
        Brain Dev. 2003; 25: 477-480
        • Dravet C.
        • Bureau M.
        • Roger J.
        Benign myoclonic epilepsy in infants.
        in: Roger J. Bureau M. Dravet C. Dreifuss F.E. Perret A. Wolf P. Epileptic syndromes in infancy, childhood and adolescence. 2nd ed. John Libbey, London1992: 67-74
        • Dravet C.
        • Bureau M.
        • Roger J.
        Severe myoclonic epilepsy in infants.
        in: Roger J. Bureau M. Dravet C. Dreifuss F.E. Perret A. Wolf P. Epileptic syndromes in infancy, childhood and adolescence. 2nd ed. John Libbey, London1992: 75-88
        • Doose H.
        Myoclonic astatic epilepsy of early childhood.
        in: Roger J. Dravet C. Bureau M. Dreifuss F.E. Wolf P. Epileptic syndromes in infancy, childhood and adolescence. 2nd ed. John Libbey, London1992: 103-114
        • Leary L.D.
        • Wang D.
        • Nordli Jr, D.R.
        • Engelstad K.
        • De Vivo D.C.
        Seizure characterization and electroencephalographic features in Glut-1 deficiency syndrome.
        Epilepsia. 2003; 44: 701-707
        • Overweg-Plandsoen W.C.
        • Groener J.E.
        • Wang D.
        • Onkenhout W.
        • Brouwer O.F.
        • Bakker D.C.
        • et al.
        GLUT-1 deficiency without epilepsy—an exceptional case.
        J Inherit Metab Dis. 2003; 26: 559-563
        • Glaser G.H.
        Hypoglycemia. The EEG in certain metabolic disorders.
        in: Glaser G.H. Handbook of electroencephalography and clinical neurophysiology, part C. vol. 15. Elsevier, Amsterdam1976: 16-17