PMID- 10227690
OWN - NLM
STAT- MEDLINE
DCOM- 19990617
LR  - 20190822
IS  - 0364-3190 (Print)
IS  - 0364-3190 (Linking)
VI  - 24
IP  - 4
DP  - 1999 Apr
TI  - Defective glucose transport across brain tissue barriers: a newly recognized
      neurological syndrome.
PG  - 587-94
AB  - Impaired glucose transport across brain tissue barriers causes infantile
      seizures, developmental delay and acquired microcephaly. Since the first report
      in 1991 (De Vivo et al, NEJM, 1991) 17 patients have been identified with the
      glucose transporter protein syndrome (GTPS). The diagnostic feature of the
      syndrome is an unexplained hypoglycorrhachia in the clinical setting of an
      infantile epileptic encephalopathy. We review our clinical experience by
      highlighting one illustrative case: a 6-year old girl who presented at age 2
      months with infantile seizures and hypoglycorrhachia. The CSF/blood glucose ratio
      was 0.33. DNA sequencing identified a missense mutation in exon 7 (C1108T).
      Erythrocyte GLUT1 immunoreactivity was normal. The time course of
      3-O-methyl-glucose (3OMG) uptake by erythrocytes of the patient was 46% that of
      mother and father. The apparent Km was similar in all cases (2-4 mmol/L), but the
      apparent Vmax in the patient was only 28% that of the parents (500 versus 1,766
      fmol/s/10(6)RBC; p < 0.004). In addition, a 3-month trial of oral thioctic acid
      also benefited the patient and increased the Vmax to 935 fmol/s/10(6) RBC (p < 3 
      x 10(-7)). Uptake of dehydroascorbic acid by erythrocytes of the patient was
      impaired to the same degree as that of 3OMG (Vmax was 38% of that of the
      mother's), which supports previous observations of GLUT1 being multifunctional.
      These studies confirm the molecular basis of the GTPS and the multifunctional
      role of GLUT1. The need for more effective treatment is compelling.
FAU - Klepper, J
AU  - Klepper J
AD  - Division of Pediatric Neurology, Columbia University, New York, NY 10032, USA.
FAU - Wang, D
AU  - Wang D
FAU - Fischbarg, J
AU  - Fischbarg J
FAU - Vera, J C
AU  - Vera JC
FAU - Jarjour, I T
AU  - Jarjour IT
FAU - O'Driscoll, K R
AU  - O'Driscoll KR
FAU - De Vivo, D C
AU  - De Vivo DC
LA  - eng
GR  - CA30388/CA/NCI NIH HHS/United States
GR  - EY-08918/EY/NEI NIH HHS/United States
GR  - NS37949-01/NS/NINDS NIH HHS/United States
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Neurochem Res
JT  - Neurochemical research
JID - 7613461
RN  - 0 (Glucose Transporter Type 1)
RN  - 0 (Monosaccharide Transport Proteins)
RN  - 0 (SLC2A1 protein, human)
RN  - 146-72-5 (3-O-Methylglucose)
RN  - IY9XDZ35W2 (Glucose)
RN  - Y2Z3ZTP9UM (Dehydroascorbic Acid)
SB  - IM
MH  - 3-O-Methylglucose/blood
MH  - Biological Transport/physiology
MH  - Brain/*metabolism
MH  - Child
MH  - Dehydroascorbic Acid/blood
MH  - Developmental Disabilities/*etiology/genetics
MH  - Erythrocytes/metabolism
MH  - Female
MH  - Glucose/*metabolism
MH  - Glucose Transporter Type 1
MH  - Humans
MH  - Immunoblotting
MH  - Microcephaly/*etiology/genetics
MH  - Monosaccharide Transport Proteins/genetics/physiology
MH  - Mutation/physiology
MH  - Spasms, Infantile/*etiology/genetics
MH  - Syndrome
EDAT- 1999/05/05 00:00
MHDA- 1999/05/05 00:01
CRDT- 1999/05/05 00:00
PHST- 1999/05/05 00:00 [pubmed]
PHST- 1999/05/05 00:01 [medline]
PHST- 1999/05/05 00:00 [entrez]
AID - 10.1023/a:1022544131826 [doi]
PST - ppublish
SO  - Neurochem Res. 1999 Apr;24(4):587-94. doi: 10.1023/a:1022544131826.