Characteristics of the test : (includes 1 gene)
SLC2A1 (OMIM #138140)
Basic characteristics of the clinical phenotype:
Idiopathic Generalized Epilepsy (IGE) - Idiopathic or "genetic" epilepsy is a common name that includes several types of epilepsy. Typical seizures are generalized absences, which include early-onset absence epilepsy (EOAE), childhood absence epilepsy (CAE), and juvenile absence epilepsy (JAE). The three diseases are difficult to distinguish from each other, but in most cases the differentiation is by age of onset. CAE begins between 4 and 10 years of age, in EOAE absence seizures appear before the fourth year of life, and in JAE - after 10 years of age.
GLUT1 deficiency syndrome (GLUT1 Deficiency) - A rare genetic disease due to a disorder of energy metabolism in the brain resulting as a result from a molecular defect in the major glucose transporter - GLUT1, encoded by the SLC2A1 gene. It is characterized by early-onset epileptic encephalopathy, acquired microcephaly, delayed neuropsychiatric development, impaired motor coordination, ataxia, confusion, sleep disturbances and headache. The onset of seizures is usually in the first 4 months of life. Typical clinical features of the disease include low levels of glucose (hypoglycorachia) and lactate in the cerebrospinal fluid due to the inability to transport glucose across the blood-brain barrier. Correct diagnosis is extremely important, because when applying a ketogenic diet there is a decrease in the frequency of seizures and improved motor function.
Genetic defects in the SLC2A1 gene occur in 12% of patients with childhood absence epilepsy. About 70-80% of patients with GLUT1 - DS carry a pathogenic point variant, while the spectrum of intragenic or deletions of the entire SLC2A1 gene is significantly smaller - 11-14%.
Reasons for referring:
All patients with absence seizures and suspected types of absence epilepsy - childhood absence epilepsy (CAE) or very early childhood epilepsy (EAE), JAE. In the presence of acquired microcephaly, decline in neuropsychological development after the onset of seizures, motor disorders in early childhood and suspicion of glucose transporter deficiency syndrome (GLUT1 syndrome).
Interpretation of results:
The detection of mutations in the SLC2A1 gene allows the diagnosis of idiopathic generalized epilepsy (IGE) in cases of lack of intellectual retardation and later onset of absence seizures, as well as GLUT1 deficiency syndrome in the presence of epileptic encephalopathy with early onset neuropsychiatric development, etc.
Genetic diagnosis allows an adequate prognosis depending on the type of mutation and the severity of the disease.
In cases of GLUT1 deficiency syndrome, it is possible to apply a ketogenic diet, leading to almost complete disappearance of epileptic seizures.
Genetic diagnosis will allow assessment of the recurrent risk for transmitting the pathogenic mutation to the future generations.
The genetic counselor will interpret and answer all questions about your result.
Method: Sanger sequencing and MLPA (Multiplex Ligation dependent Probe Amplification)
The method involves bidirectional DNA sequencing of all coding exons and intron-exon boundaries of the SLC2A1 gene. The laboratory offers single exon sequencing in relatives of patients to determine the carrier status in cases where the SLC2A1 mutation is known (Test № 182).
MLPA analysis is a semi-quantitative method for determining copy number variations of DNA. The methodology is used to detect intragenic or whole-gene deletions or duplications. The analysis for searching for large SLC2A1 gene deletions or insertions is performed using the kit SALSA MLPA probemix P138-C1 SLC2A1-STXBP1, developed by MRC-Holland (Amsterdam, Holland).
Sensitivity of the method: Sanger sequencing - 99.5%; MLPA – 90%
What does the test involve?
• DNA isolation and sample storage.
• Direct sequencing of target genes / gene regions in search of point mutations and MLPA analysis of target genes / gene regions to detect pathogenic copy number variations.
• Forming a written result from the genetic test.
• Diagnostic interpretation of results and genetic counseling.
Biological material: Venous blood or DNA
For more information, please read "Biological Sample Requirements and Transport Information" carefully.
