There are three protein components to the hexosaminidase complexes: the alpha subunit, the beta subunit, and the GM2 ganglioside activator protein. Deficiency of the alpha subunit, due to mutations in the HEXA gene, results in deficiency of the hexosaminidase A complex and causes Tay-Sachs disease. Deficiency of the beta subunit, due to mutations in the HEXB gene, results in deficiency of both the beta-hexosaminidase A and B complexes and causes Sandhoff disease. Deficiency of the GM2 ganglioside activator protein, due to mutation in the GM2A gene, is associated with the rare AB variant form of GM2 gangliosidosis. Enzymatic analysis can distinguish between the GM2 gangliosidoses. Clinically, these diseases are indistinguishable.
Mutations in the HEXA gene cause Tay-Sachs disease. Targeted mutation detection can be performed to test for mutations common in the Ashkenazi Jewish population. For mutations not identified by this panel, sequencing of the HEXA gene must be performed. Diagnostic sequencing analysis of the HEXA gene coding region is available for Tay-Sachs disease patients and their at-risk relatives on a clinical basis. For patients with mutations not identified by full gene sequencing, a separate deletion/duplication assay is available using a targeted CGH array NH.
For questions about testing for Tay-Sachs disease, call EGL Genetics at 470-378-2200 or 855-831-7447.
For further clinical information about lysosomal storage diseases, including management and treatment, call the Emory Lysosomal Storage Disease Center at (404) 778-8565 or (800) 200-1524.
1). Kaback, M., J. Lim-Steele, D. Dabholkar, D. Brown, N. Levy, and K. Zeiger, Tay-Sachs disease--carrier screening, prenatal diagnosis, and the molecular era. An international perspective, 1970 to 1993. The International TSD Data Collection Network. JAMA, 1993. 270(19): p. 2307-15.
- Confirmation of a clinical diagnosis of Tay Sachs Disease.
- Follow up of individuals with a positive/borderline biochemical carrier screening test.
- Prenatal testing for known familial mutations.
- Assessment of carrier status in high risk family members with known mutation analysis.
Clinical Sensitivity: 94 - 98% 
Analytical Sensitivity: ~99%
Prevalence: The estimated prevalence of all lysosomal storage disorders is 2-5 per 100,000. The prevalence of Tay-Sachs disease varies by ethnicity and is highest in the Ashkenazi Jewish population (1 in 3600), in French Canadians, in Cajuns from Louisiana, and in the Old Order Amish in Pennsylvania. The prevalence in other populations is approximately 1 in 250,000.
Submit only 1 of the following specimen types
Preferred specimen type: Whole Blood
Type: Whole Blood
Specimen Requirements:In EDTA (purple top) tube:
Infants (<2 years): 2-3 ml
Children (>2 years): 3-5 ml
Older Children & Adults: 5-10 ml
Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overnight delivery.
Specimen Requirements:OrageneTM Saliva Collection kit (available through EGL) used according to manufacturer instructions.
Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.
- Ashkenazi Jewish Carrier Screen (AJ) is available using targeted mutation analysis.
- Mutation Analysis for Pseudodeficiency Allele may be available upon request.
- HEX A Enzyme Assay (HA) is available to establish a biochemical diagnosis.
- Sequencing of HEXB Gene (DA).
- Lysosomal Enzyme Screening Panel (LS).
- Tay Sachs Disease Deletion/Duplication Assay is available separately for individuals where mutations are not identified by sequence analysis. Refer to the test requisition or contact the laboratory for more information.
- Custom Diagnostics Known Mutation Analysis (KM) is available to test family members.
- Prenatal testing is available to couples who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.