Description:
GLUT1 DEFICIENCY SYNDROME 1; GLUT1DS1
SOLUTE CARRIER FAMILY 2 (FACILITATED GLUCOSE TRANSPORTER), MEMBER 1; SLC2A1
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases
PIGI Consented Sample |
| Quantity |
25 µg |
| Quantitation Method |
Please see our FAQ |
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Biopsy Source
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Peripheral vein
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Cell Type
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B-Lymphocyte
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Tissue Type
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Blood
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Transformant
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Epstein-Barr Virus
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Sample Source
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DNA from LCL
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Race
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White
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Ethnicity
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Not Hispanic/Latino
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Ethnicity
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Italian; German; English
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Country of Origin
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USA
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Family Member
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1
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Family History
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N
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Relation to Proband
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proband
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by LINE assay |
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| Gene |
SLC2A1 |
| Chromosomal Location |
1p34.2 |
| Allelic Variant 1 |
p.Thr295Lys (T295K); GLUT1 DEFICIENCY SYNDROME 1 |
| Identified Mutation |
c.884 C>A (T295K); GLUT1 deficiency syndrome-1 is a neurologic disorder showing wide phenotypic variability. The most severe 'classic' phenotype comprises infantile-onset epileptic encephalopathy associated with delayed development, acquired microcephaly, motor incoordination, and spasticity. Onset of seizures, usually characterized by apneic episodes, staring spells, and episodic eye movements, occurs within the first 4 months of life. Other paroxysmal findings include intermittent ataxia, confusion, lethargy, sleep disturbance, and headache. Varying degrees of cognitive impairment can occur, ranging from learning disabilities to severe mental retardation. Hypoglycorrhachia (low CSF glucose, less than 40 mg/dl) and low CSF lactate are essentially diagnostic for the disorder. As more cases with GLUT1 deficiency syndrome were described, the phenotype was broadened to include individuals with ataxia and mental retardation but without seizures, individuals with dystonia and choreoathetosis, and rare individuals with absence seizures and no movement disorder. The disorder, which results from a defect in the GLUT1 glucose transporter causing decreased glucose concentration in the central nervous system, is part of a spectrum of neurologic phenotypes resulting from GLUT1 deficiency. GLUT deficiency syndrome-2 (612126) represents the less severe end of the phenotypic spectrum and is associated with paroxysmal exercise-induced dystonia with or without seizures. Correct diagnosis of GLUT1 deficiency is important because a ketogenic diet often results in marked clinical improvement of the motor and seizure symptoms (reviews by Pascual et al., 2004 and Brockmann, 2009). |
| Remarks |
Clinically affected; opsoclonus at 4-5 months which stopped after 1 year of age; grand mal seizure at 9 months; whole body paralysis and jerky movements of the body while remaining conscious; global developmental delays; did not walk until 22 months of age; severe lower extremity and axial body weakness; severe speech dysfluency; moderate ataxia; mild intellectual impairment; fine motor delay; fatigue; gross motor delay; seizures; cognitive delay; left sided hemiparesis and full body paralysis became episodic, resembling strokes; recovery of events is often unduly prolonged, lasting, on occasion, even weeks; regression apparent during postictal long phrase; early stiffening of the posterior leg and compartment tendons in joints; dysarthria; tendon reflexes- abnormal, brisk; plantar response- upgoing, bilateral; gait and stance- ataxic; exon sequencing identified donor was heterozygous for c.884 C>A (p.T295K) in the SLC2A1 gene that is likely a pathogenic variant; donor was also heterozygous for the following variants that are considered likely benign: c.4283 C>G (p.A1428G) in the SPTAN1 gene and c.3889 G>A (p.A1297T) in the TSC2 gene; medications: Keppra, Lamictal, Citra 2 (bicarb), Prevacid; diet- ketogenic 3:1 ratio since age 3; physical therapy; occupational therapy; speech language therapy; unaffected mother (GM27134) and unaffected father (GM27135). |
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