Neuropediatrics 2009; 40(5): 207-210
DOI: 10.1055/s-0030-1248264
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© Georg Thieme Verlag KG Stuttgart · New York

Autosomal Recessive Inheritance of GLUT1 Deficiency Syndrome

J. Klepper1 , H. Scheffer2 , M.F. Elsaid3 , E.-J. Kamsteeg2 , M. Leferink2 , T. Ben-Omran4
  • 1Childrens’ Hospital Aschaffenburg, Aschaffenburg, Germany
  • 2Department of Human Genetics,University Medical Center Nijmegen, Nijmegen, The Netherlands
  • 3Department of Pediatrics, Pediatric Neurology, Hamad Medical Corporation and Weill Cornell Medical College, Doha, Qatar
  • 4Clinical and Metabolic Genetics, Hamad Medical Corporation and Weill Cornell Medical College, Doha, Qatar
Further Information

Publication History

received 24.07.2009

accepted 20.01.2010

Publication Date:
10 March 2010 (online)


GLUT1 deficiency syndrome (GLUT1DS) is understood as a monogenetic disease caused by heterozygous SLC2A1 gene mutations with autosomaldominant and sporadic transmission. We report on a six-year-old girl from an inbred Arab family with moderate global developmental delay, epilepsy, ataxia, hypotonia, and hypoglycorrhachia (CSF glucose 36 mg/dL; CSF lactate 1.09 mmol/L; CSF/blood glucose ratio 0.44). Molecular analysis of the SLC2A1 gene identified a novel homozygous c1402C>T (p. Arg468Trp) mutation in exon 10 in the index patient and her asymptomatic younger sister. The mutation was absent in 120 control alleles of healthy individuals as well as in 400 alleles of other GLUT1DS patients. Arg468 represents a highly conserved, functionally important amino acid residue in the GLUT1 carboxy-terminus essential for substrate recognition and transport. Both unaffected parents were heterozygous for the mutation. A younger brother and two family members were healthy and carried the GLUT1 wild type. A ketogenic diet effectively controlled seizures in the index patient. We conclude that GLUT1DS can be transmitted as an autosomal recessive disease and provide new insights into genetic counselling for this treatable disorder.


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PD Dr. med. Joerg Klepper

Childrens’ Hospital Aschaffenburg

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