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 HEXB gene cause Sandhoff disease. There have been more than 25 different mutations identified in the HEXB gene. The most common mutation deletes a large segment of DNA near the beginning of the HEXB gene, which results in a total loss of enzyme activity. Diagnostic sequencing analysis of the HEXB gene coding region in addition to analysis for the common 16kb deletion is available for patients with Sandhoff disease 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 NG.
For questions about testing for Sandhoff disease, call the Emory Genetics Laboratory at (404) 778-8500 or (800) 366-1502.
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). O'Dowd, B. et al. Molecular heterogeneity in the infantile and juvenile forms of Sandhoff disease (O-variant GM2 gangliosidosis). J. Biol. Chem. 261: 12680-12685, 1986.
Analytical Sensitivity: ~99%
Prevalence: The estimated prevalence of all lysosomal storage disorders is 2-5 per 100,000. The prevalence of Sandhoff is not specifically known, but is likely to be rare and may vary by ethnicity.
Submit only 1 of the following specimen types
Preferred specimen type: Whole Blood
Type: Whole Blood
Specimen Requirements:In EDTA (purple top) or ACD (yellow 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.
- Sequencing of HEXA Gene (DD).
- Lysosomal Enzyme Screening Panel (LS).
- Custom Diagnostics Known Mutation Analysis (KM) is available to test family members.
- Sandhoff Disease Gene Deletion/Duplication Assay(NG) 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.
- 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.