Glucose Transporter Protein Syndrome

Glucose transporter type 1 deficiency syndrome (Glut1-DS) typically presents in early infancy with seizures refractory to anticonvulsants, a variety of additional neurological manifestations (e.g., spasticity, ataxia), deceleration of head growth, and delays in mental and motor development.

Glut1-DS is an autosomal dominant condition caused by mutations in the SLC2A1 gene, the only gene known to be associated with this disorder. Probands with Glut1-DS often have the condition as a result of a de novo mutation.

1. Confirmation of diagnosis: 
   All 3 of the criteria below (a, b and c) must be met to request diagnostic testing. 
   A completed Glut1-DS Supplemental Information Form must be received before testing will proceed.
   1. GLUT1-DS Phenotype:
      1. Classical
         1. Epilepsy (particularly if refractory to ≥ 2 anti-epileptic drugs)
            AND
            Developmental delay / intellectual disability 
      2. Atypical
         1. Absence seizures with early onset (< 4 years of age)
            OR 
         2. Paroxysmal exercise-induced dyskinesia
            OR 
         3. Ataxia and/or hyperkinetic movement disorder
            AND
            Developmental delay / intellectual disability
            AND
            One or more of: epilepsy, migraine, microcephaly, positive family history
   2. CSF glucose ≤ 2.5 mmol/L AND CSF:fasting serum glucose ratio < 0.6
   3. Test requested by a Neurologist or a Biochemical Diseases specialist.

      Cases that do not meet all criteria may be reviewed with Dr. Michelle Demos (mdemos[at]cw.bc.ca) or Dr. Sylvia Stockler (sstockler[at]cw.bc.ca) for further consideration.  
       

2. Carrier testing: 
   1. Although this is an autosomal dominant condition, carrier testing may be relevant to identify non-penetrant / variably-expressive mutation carriers. The familial mutation must be known.
       
3. Prenatal testing (prenatal diagnosis requests are not normally accepted from physicians other than Medical Geneticists):
   1. Pregnancies at risk of GLUT1-DS and the familial mutation is known.

Bidirectional Sanger sequencing of the entire coding region and flanking intronic sequences of the SLC2A1 gene. Deletion/duplication analysis of SLC2A1 (by multiplex ligation-probe amplification – MLPA) is performed if sequencing is negative.

NM_006516.2 The ‘A’ within the initiation codon, ATG, is designated as nucleotide number 1.

Pregnancy-related/Prenatal

If pregnancy management will be altered, 3 weeks; otherwise, routine TAT.

Blood: 4 mL EDTA is optimal (Minimum: 1 mL EDTA)
DNA: 100 μL at 200 ng/μL is optimal (Minimum: 30 μL at 200 ng/μL)

NOTE: DNA is only accepted for requests for sequencing analysis.  If MLPA is required, EDTA blood must be collected.

Label each sample with three patient identifiers; preferably patient name, PHN, and date of birth and ship to the address below. Samples should be shipped at room temperature with a completed MGL Requisition to arrive Monday to Friday (not on Canadian statutory holidays). 

Prenatal Specimens
Prenatal testing REQUIRES LABORATORY CONSULTATION PRIOR TO THE PROCEDURE and can only be ordered by a Medical Geneticist. Contact the laboratory at 604-875-2852 and choose the appropriate option for the Molecular Geneticist on service.
Chorionic Villi: 20 mg.
Direct Amniotic fluid: 25 mL collected in two separate tubes of equal volume.
Cultured Amniocytes: Two (2) 100% confluent T-25 flasks.
DNA extracted from prenatal specimens: 100 μL at 200 ng/μL is optimal (Minimum: 30 μL at 200 ng/μL)

Label each sample with three patient identifiers; preferably patient name, PHN, and date of birth. Ship samples by overnight courier with a completed MGL Requisition to arrive Monday to Friday (not on Canadian statutory holidays) as follows:

• Villi – on wet ice or in media at room temperature
• Amniocytes, Amniotic fluid, DNA – at room temperature

A completed Glut1-DS Supplemental Information Form MUST accompany the requisition. 

Testing is only available to residents of Canada, except in very specific circumstances where testing is urgent or emergent.  Payment is not required when requests are made for individuals who are insured by Health Insurance BC (administered through the BC Medical Services Plan (MSP)) AND eligible for testing according to the test utilization guidelines / policy. If the individual undergoing testing is not insured by these providers or does not meet utilization guidelines or policy, please complete a billing form; testing will only commence after receipt of billing informationTest prices can be found here.

Molecular genetic testing is limited by the current understanding of the genome and the genetics of a particular disease, as well as by the method of detection used. This method will not detect all mutations (e.g., promoter mutations, regulatory element mutations).

For carrier/predictive testing due to family history, it is generally important to first document the gene mutation in an affected or carrier family member. This information should be provided to the laboratory for assessment of whether the assay is appropriate for detection of the familial mutation, and to aid in the interpretation of data.

In some cases, DNA alterations of undetermined or unclear clinical significance may be identified.

Rare single nucleotide variants or polymorphisms could lead to false-negative results. If results obtained do not match the clinical findings, consult the on-service Molecular Geneticist.

A previous bone marrow transplant from an allogenic donor will result in molecular data that reflects the donor genotype rather than the recipient (patient) genotype. Consult the on-service Molecular Geneticist for approach to testing in such individuals.

Transfusions performed with packed red blood cells will generally not affect the outcome of molecular genetic testing. However, if there is no clinical urgency, the cautious approach is to wait one week post packed red cell transfusion before collecting a sample for genetic testing. Consult the on-service Molecular Geneticist as needed.

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.