GM27137

GM27137 LCL from B-Lymphocyte

Description:

GLUT1 DEFICIENCY SYNDROME 1; GLUT1DS1
SOLUTE CARRIER FAMILY 2 (FACILITATED GLUCOSE TRANSPORTER), MEMBER 1; SLC2A1

Affected:

Yes

Sex:

Male

Age:

6 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
PIGI Consented Sample

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

LCL from B-Lymphocyte

Race

White

Ethnicity

Not Hispanic/Latino

Ethnicity

Italian; German; English

Country of Origin

USA

Family Member

Family History

Relation to Proband

proband

Species

Homo sapiens

Common Name

Human

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).

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by LINE assay

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).