The Invitae Glucose Transporter Type 1 Deficiency Syndrome Test analyzes the SLC2A1 gene, whose pathogenic variants cause glucose transporter type 1 deficiency syndrome (GLUT1DS), which is associated with low glucose concentration in the cerebrospinal fluid and related neurometabolic symptoms. Genetic testing of this gene may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives.
The also offers broad epilepsy panel that have been designed to provide a genetic analysis of epilepsy disorders. Depending on the individual’s clinical and family history, one of these broader panels may be appropriate as an alternative to this test. They can be ordered at no additional cost.
Glucose transporter type 1 deficiency syndrome (GLUT1DS)
The SLC2A1 gene encodes the glucose transporter type 1 protein (Glut1), which is responsible for glucose transport across the blood-brain barrier to meet the energy demands of the brain. Pathogenic variants in SLC2A1 disrupt Glut1 protein function and cause GLUT1DS.
GLUT1DS is a treatable neurometabolic disorder. The biochemical hallmark of GLUT1DS is hypoglycorrhachia (low glucose concentration in the cerebrospinal fluid) with normal blood-glucose level. Neurological symptoms may be categorized into three domains: seizures, movement disorders, and cognitive or behavioral disturbances. The classic GLUT1DS phenotype is characterized by persistent symptoms involving all three domains. Patients with milder phenotypes may manifest intermittent or persistent symptoms in only one or two domains.
The classic phenotype of GLUT1DS includes infantile-onset seizures, developmental delay, acquired microcephaly, and complex movement disorders. Seizures vary in frequency, severity, and types and may include generalized tonic or clonic, focal, myoclonic, atypical absence, atonic, and unclassified seizures. GLUT1DS-associated seizures are usually refractory to anticonvulsants but can often be substantially improved with a ketogenic diet. Patients are sensitive to fasting or exertion and typically develop cognitive impairment that ranges from learning disabilities to severe intellectual disability. Patients with milder forms of epilepsy, with non-epileptic syndromes that are characterized by both persistent and paroxysmal movement disorders, and with varying degrees of cognitive impairment have also been recognized.
SLC2A1 is the only gene in which pathogenic variants are known to cause GLUT1DS. More than 95% of the patients with symptoms consistent with this condition will have a pathogenic variant in the SLC2A1 gene.
The vast majority of identified GLUT1DS patients have one de novo pathogenic variant in the SLC2A1 gene. The disease is primarily inherited in an autosomal dominant manner, although rare cases of autosomal recessive transmission have been reported.
The estimated prevalence of GLUT1DS in Queensland, Australia, is approximately 1 in 90,000. A point prevalence of GLUT1DS in Norway was estimated at 2.6 in 1,000,000 inhabitants. These rates are likely underestimated because ascertainment of cases is biased by physician awareness of this condition.
Patients with clinical symptoms of GLUT1DS or hypoglycorrhachia with a lumbar puncture showing a low CSF glucose level (< 60mg/dL absolute value) and a normal blood-glucose level are candidates for this test. Particularly good candidates are patients who also show a reduced erythrocyte glucose uptake in the 3-O-methyl-D-Glucose assay. Testing of additional family members of a patient with a known pathogenic SLC2A1 may be warranted.
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.
Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|