Tay-Sachs disease: A progressive neurodegenerative disorder caused by intralysosomal storage of the specific glycosphingolipid GM2 ganglioside. Affected individuals generally die before the age of 4 years. The carrier frequency of this disorder in the Ashkenazi Jewish population is 1/30.

Fanconi anemia type C: A condition characterized by congenital anomalies, aplastic anemia and an increased risk of malignancies. The carrier frequency of this disorder in the Ashkenazi Jewish population is 1/90.

Canavan disease: Characterized by macrocephaly, lack of head control, developmental delays by the age of three to five months, severe hypotonia, and failure to achieve independent sitting, ambulation, or speech. Affected individuals generally live into their teens. The carrier frequency of this disorder in the Ashkenazi Jewish population is 1/40.

Familial dysautonomia: Characterized by gastrointestinal dysfunction, vomiting crises, recurrent pneumonia, altered sensitivity to pain and temperature perception, and cardiovascular instability. The carrier frequency of this disorder in the Ashkenazi Jewish population is 1/30.

All of these conditions have an autosomal recessive inheritance pattern. These conditions have an increased incidence in the Ashkenazi Jewish population, relative to other populations, due to founder mutations. 

In patients of Ashkenazi Jewish ancestry, these mutations account for 98% of Canavan disease alleles; over 99% of Familial dysautonomia alleles; greater than 90% of Fanconi anemia alleles; and 95% of Tay-Sachs disease alleles.

A completed AJ Carrier & Tay Sachs Enzyme Screening Supplemental Info Form must be received before testing will proceed.

1. Carrier testing:
   1. BOTH members of the couple MUST BE or MAY BE of Ashkenazi Jewish ancestry.  If the couple is NOT pregnant, testing should be sequential (a negative result in one member sufficiently reduces the risk such that additional testing is unnecessary).

NOTE: All four conditions are tested and reported; individual tests cannot be requested.  If a couple wishes Tay-Sachs screening only, see AJ Carrier & Tay Sach Enzyme Screening Algorithm.  

1. This test is not indicated for:
   1. Individuals of Ashkenazi Jewish ancestry whose partner is non-Ashkenazi (non-Jewish or Sephardi) (i.e. mixed couples). 
   2. Individuals of Sephardi Jewish or French Canadian ancestry seeking carrier screening for Tay-Sachs disease. 

See AJ Carrier & Tay Sachs Enzyme Screening Algorithm and the SOGC/CCMG Clinical Practice Guideline for further details.

     2. This test is not indicated for children who have not yet reached reproductive age.

     3. This test cannot distinguish homozygotes from heterozygotes and so is not generally useful for diagnostic testing or prenatal diagnosis; consult the on-service Molecular Geneticist. 

The Elucigene Ashplex 1 Assay (Gen-Probe, Inc) is used to assess the c.1274_1277dup, c.805G>A and c.1421+1G>C mutations in the HEXA gene; the c.693C>A and c.854A>C mutations in the ASPA gene; the c.2087G>C and the c.2204+6T>C mutations in the IKBKAP gene; and the c.456+4A>T mutation in the FANCC gene. The normal sequence is not assessed; detection of a mutation in the context of carrier screening is interpreted as heterozygosity for the mutation. Individual mutations/conditions can not be independently tested.

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)

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). 

A completed AJ Carrier & Tay Sachs Enzyme Screening Supplemental Info 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., mutations outside the regions tested as described above, large genomic deletions, 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 rare 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.