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Glut‐1 deficiency syndrome: Clinical, genetic, and therapeutic aspects
Author(s) -
Wang Dong,
Pascual Juan M.,
Yang Hong,
Engelstad Kristin,
Jhung Sarah,
Sun Ruo Peng,
De Vivo Darryl C.
Publication year - 2005
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20331
Subject(s) - cerebrospinal fluid , genotype , medicine , epilepsy , endocrinology , missense mutation , nonsense mutation , ketogenic diet , microcephaly , heterozygote advantage , phenotype , genetics , biology , pediatrics , gene , psychiatry
Impaired glucose transport across the blood‐brain barrier results in Glut‐1 deficiency syndrome (Glut‐1 DS, OMIM 606777), characterized by infantile seizures, developmental delay, acquired microcephaly, spasticity, ataxia, and hypoglycorrhachia. We studied 16 new Glut‐1 deficiency syndrome patients focusing on clinical and laboratory features, molecular genetics, genotype–phenotype correlation, and treatment. These patients were classified phenotypically into three groups. The mean cerebrospinal fluid glucose concentration was 33.1 ± 4.9mg/dl equal to 37% of the simultaneous blood glucose concentration. The mean cerebrospinal fluid lactate concentration was 1.0 ± 0.3mM, which was less than the normal mean value of 1.63mM. The mean V max for the 3‐ O ‐methyl‐ D ‐glucose uptake into erythrocytes was 996 fmol/10 6 red blood cells per second, significantly less (54 ± 11%; t test, p < 0.05) than the mean control value of 1,847. The mean Km value for the patient group (1.4 ± 0.5mM) was similar to the control group (1.7 ± 0.5mM; t test, p > 0.05). We identified 16 rearrangements, including seven missense, one nonsense, one insertion, and seven deletion mutations. Fourteen were novel mutations. There were no obvious correlations between phenotype, genotype, or biochemical measures. The ketogenic diet produced good seizure control. Ann Neurol 2005;57:111–118