Mutations in the HEXA and HEXB genes cause Tay Sachs disease and Sandhoff disease, respectively. These two diseases are distinguished biochemically by enzymatic analysis of β-hexosaminidase A (a heterodimer of the alpha and beta subunits), that is deficient in Tay Sachs and β-hexosaminidase B (a homodimer of two beta subunits), that is deficient in Sandhoff’s disease. β-hexosaminidase A and β-hexosaminidase B enzyme activities are normal in GM2 gangliosidosis AB variant.
Mutations in the GM2A gene (5q33.1) cause the rare GM2 gangliosidosis AB variant (GM2 AB variant) due to the deficiency of the GM2 activator protein and are inherited in an autosomal recessive manner. The clinical course of GM2 AB variant is similar to that of a patient with classic Tay Sachs disease. Disease onset usually occurs after five or six months of age and follows a neurodegenerative course with features including delayed motor milestones, hypotonia, macular cherry red spots, and abnormal MRI findings.
Sequence analysis of the entire GM2A gene coding region is available for individuals suspected of having GM2 AB variant and their at-risk relatives on a clinical basis.
- Confirmation of a clinical diagnosis of GM2-gangliosidosis AB variant.
- Carrier testing in adults with a family history of GM2-gangliosidosis AB variant.
Analytical Sensitivity: ~99%
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.
- Custom diagnostic mutation analysis (KM) is available to family members if mutations are identified by targeted mutation testing or sequencing analysis.
- Prenatal testing is available only for known familial mutations to individuals who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.
- For confirmation purposes, if two mutations or variants of unknown clinical significance are identified, glycolipids in CSF can be performed on a research basis.