title: An infant with pseudohyperkalemia, hemolysis, and seizures: cation-leaky GLUT1-deficiency syndrome due to a SLC2A1 mutation.
abstract: BACKGROUND
  GLUT1 (glucose transporter 1) deficiency syndrome is a well-known presentation in pediatric practice. Very rare mutations not only disable carbohydrate transport but also cause the red cell membrane to be constitutively permeant to monovalent cations, namely sodium and potassium.
  
  
  OBJECTIVE
  The aim of this study was to describe the pediatric presentation of a patient with GLUT1 deficiency with such a cation-leaky state.
  
  
  METHODS
  The infant presented with erratic hyperkalemia, neonatal hyperbilirubinemia, anemia, hepatic dysfunction, and microcephaly. Later, seizures occurred and developmental milestones were delayed. Magnetic resonance imaging and computerized tomography scans of the brain showed multiple abnormalities including periventricular calcification. Visual impairment was present due to the presence of both cataracts and retinal dysfunction.
  
  
  RESULTS
  Measurements of red cell cation content showed extremely leaky red cells (causing the hemolysis) and temperature-dependent loss of potassium from red cells (explaining the hyperkalemia as pseudohyperkalemia). A trinucleotide deletion in SLC2A1, coding for the deletion of isoleucine 435 or 436 in GLUT1, was identified in the proband.
  
  
  CONCLUSIONS
  This is the fourth pedigree to be described with this most unusual syndrome. The multisystem pathology probably reflects a combination of glucose transport deficiency at the blood-brain barrier (as in typical GLUT1 deficiency) and the deleterious osmotic effects of a cation-leaky membrane protein in the cells where GLUT1 is expressed, notably the red cell. We hope that this detailed description will facilitate rapid diagnosis of this disease entity.
authors.affiliation: Division of Medicine, University College London, Rayne Building, University Street, London WC1E 6JF, United Kingsom.
authors.forename: Waleed M
authors.initials: WM
authors.lastname: Bawazir
authors.forename: Evelien F
authors.initials: EF
authors.lastname: Gevers
authors.forename: Joanna F
authors.initials: JF
authors.lastname: Flatt
authors.forename: Ai Leen
authors.initials: AL
authors.lastname: Ang
authors.forename: Benjamin
authors.initials: B
authors.lastname: Jacobs
authors.forename: Caroline
authors.initials: C
authors.lastname: Oren
authors.forename: Stephanie
authors.initials: S
authors.lastname: Grunewald
authors.forename: Mehul
authors.initials: M
authors.lastname: Dattani
authors.forename: Lesley J
authors.initials: LJ
authors.lastname: Bruce
authors.forename: Gordon W
authors.initials: GW
authors.lastname: Stewart
mesh_terms: D004827:Epilepsy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004913:Erythrocytes, Abnormal / Q000378:metabolism; D005260:Female; D051272:Glucose Transporter Type 1 / Q000172:deficiency* / Q000235:genetics*; D006461:Hemolysis / Q000235:genetics*; D006801:Humans; D006947:Hyperkalemia / Q000235:genetics* / Q000378:metabolism; D007223:Infant; D008279:Magnetic Resonance Imaging; D011188:Potassium / Q000378:metabolism; D013577:Syndrome
chemical_list: D051272:Glucose Transporter Type 1; C495677:SLC2A1 protein, human; D011188:Potassium