Tay-Sachs Disease Carrier Testing

Clinical Use

Use

This test provides enzymatic analysis of Hexosaminidase A in leukocytes for the screening of carriers of Tay-Sachs disease and Sandhoff disease. Tay-Sachs disease is an autosomal recessive disorder characterized by progressive deterioration of the nervous system, with symptomatic onset in infancy and a fatal prognosis. Sandhoff disease, closely related, presents similarly but with high HexA activity. Individuals with a family history, those of Ashkenazi Jewish, French Canadian, or Cajun descent, and those planning a pregnancy or using oral contraceptives should consider this test. Carriers generally show low activity of HexA and total hexosaminidase, and while a negative result decreases the risk of having an affected child, it does not eliminate it entirely. Follow-up molecular testing may clarify carrier status after presumptive screening.

Special Instructions

This test is indicated for individuals planning a pregnancy or those with a family history of Tay-Sachs disease, particularly among high-risk populations such as Ashkenazi Jews and Cajun descendants. Patients taking oral contraceptives are also advisable for testing due to a heightened risk for false positive results in serum testing. The test includes enzymatic analysis followed by potential molecular genetic testing for conclusive carrier status identification.

Limitations

The assay may yield false positive results due to pseudodeficiency alleles leading to normal appearing HEXA activity. Certain genetic variants such as AB and B1 variants may not be detectable by this screening method, potentially resulting in true carriers being missed. Molecular genetic confirmation is recommended for final assessment of carrier status. Only a small number of individuals are affected by this phenomenon, but it emphasizes the need for careful interpretation of results and, if necessary, retesting.

Test Details

New York Approved