Tay-Sachs Plus
Tay-Sachs Disease is an autosomal recessive lysosomal storage disorder caused by mutations in the HEXA gene, which codes for the alpha subunit of the Hexosaminidase A enzyme.
PrintTay-Sachs Disease is an autosomal recessive lysosomal storage disorder caused by mutations in the HEXA gene, which codes for the alpha subunit of the Hexosaminidase A enzyme.
Deficiency of the enzyme causes accumulation of GM2 ganglioside, mainly in the brain, that leads to neurological deterioration. More than 100 disease-causing mutations have been described, with increased carrier frequencies in Ashkenazi Jewish, Cajun, French-Canadian,and Irish-American populations.
Ambry Genetics requires enzyme analysis prior to Tay-Sachs Plus for carrier and diagnostic tests. Full gene sequence analysis can detect over 100 previously-described HEXA disease-causing mutations. Together, enzyme analysis and Tay-Sachs Plus tests provide the highest possible sensitivity and specificity.
The Ambry Test: Tay-Sachs Plus is a full gene sequence analysis of HEXA that includes detection of the 7.6 kb French-Canadian deletion and two pseudodeficiency mutations. Approximately 99% of HEXA mutations are detectable by Tay-Sachs Plus.
Tay-Sachs Disease is an autosomal recessive lysosomal storage disorder caused by mutations in the HEXA gene, which codes for the alpha subunit of the Hexosaminidase A enzyme. Deficiency of the enzyme causes accumulation of GM2 ganglioside, mainly in the brain, that leads to neurological deterioration. Most Tay-Sachs cases are the rapidlyprogressive infantile type with onset of weakness, seizures, and blindness beginning at age 3-6 months. Late onset Tay-Sachs with childhood or early adult presentation is caused by HEXA mutations that allow residual Hex A enzyme activity. More than 100 disease-causing mutations have been described, with increased carrier frequencies found in Ashkenazi Jewish, Cajun, French-Canadian, and Irish-American populations.
Enzyme analysis is a sensitive carrier screening and diagnostic tool that should be used in all cases. However, Tay-Sachs Plus serves as a valuable complement for:
- resolution of indeterminate or pseudodeficient Tay-Sachs enzyme results: approximately 36% of enzymaticallydefined non-Ashkenazi Jewish and 2% of Ashkenazi Jewish “carriers” are actually pseudodeficiency mutation carriers with no increased risk for affected children1
- diagnostic clarification in patients with Tay-Sachs symptoms and inconsistent enzyme results
- mutation identification in affected patients
Ambry Genetics requires enzyme analysis prior to Tay-Sachs Plus for carrier and diagnostic tests. Full gene sequence analysis can detect the 100+ described HEXA mutations. Together these tests provide the highest possible sensitivity and specificity.
The following table shows revised or post-test carrier risks by ethnicity, assuming a negative Ambry Test result and no family history of the disease. Risks shown exclude consideration of enzyme analysis results.
| Ethnicity | Tay-Sachs Carrier Risk before Test | Revised Carrier Risk after Tay-Sachs Plus |
| Ashkenazi Jewish, Cajun, French-Canadian | 1/302,3 | 1/2901 |
| Irish-American | 1/444 | 1/4301 |
| Other populations at general risk | 1/2801,4 | 1/27,901 |
The Tay-Sachs Plus test is a full gene sequence analysis that includes detection of the 7.6 kb French-Canadian deletion and two pseudodeficiency mutations. PCR-based double-stranded automated sequencing is performed in the sense and antisense directions for exons 1-14 of the HEXA gene, plus at least 20 bases into the 5’ and 3’ ends of all the introns. A bridge-PCR is also performed to detect the presence of the 7.6kb deletion by yielding PCR product only when the deletion is present. Specific mutation analysis for individual HEXA mutations known to be in the family is also available.
Approximately 99% of HEXA mutations are detectable by Tay-Sachs Plus regardless of the patient’s ethnicity.
BLOOD: Collect 3-5 cc from adult or 2 cc minimum from child into EDTA purple-top tube (first choice) or ACD yellow-top tube (second choice). Store at room temperature or refrigerate. Ship at room temperature.
BLOOD SPOT: Minimum of one complete spot approximately 0.5 inch in diameter on S&S 903 collection paper or similar. Store in a clean plastic bag at room temperature. Ship at room temperature.
SALIVA: Collect 2 ml into Oragene™ DNA Self-Collection container. Store and ship at room temperature.
DNA: Send 20 µg in TE at 50-100 ng/µl. Store frozen and ship on ice or dry ice.
PRENATAL: Prenatal testing is available. Please call an Ambry Genetic Counselor to discuss your case.
| Test Code | Technique | CPT Codes |
|---|---|---|
| 1240 | Tay-Sachs Plus (HEXA gene sequence) | 83891x1, 83894x16, 83898x15, 83904x28, 83909x28, 83912x1 |
| 5240 | Tay-Sachs Enzyme (HEXA Leukocyctes) | 83080x1, 83912x1 |
| Technique | Days |
|---|---|
| Tay-Sachs Plus (HEXA gene sequence) | 10-21 |
| Tay-Sachs Enzyme (HEXA Leukocyctes) |
1 Kaback M et al. JAMA. 1993;270;2307-2315.
2 Kaplan F. Genet Test. 1998;2(4):271-292.
3 March of Dimes Birth Defects Foundation. Genetic Screening Pocket Facts. 2001.
4 Branda KJ et al. Genet Test. 2004;8(2):174-180.