Tay-Sachs disease (TSD) is a recessively inherited neurodegenerative disorder caused by a deficiency of beta-hexosaminidase A that leads to a pathological accumulation of GM2 ganglioside. Features include progressive loss of coordination, seizures, difficulty swallowing and poor pulmonary function. Affected individuals eventually become blind, severely mentally retarded, paralyzed and unaware of their surroundings. Onset is typical at approximately 6 months of age, and average life expectancy is 3-5 years. TSD is most prevalent among Ashkenazi Jews with the carrier frequency estimated to be 1 in 30. The American College of Obstetricians and Gynecologists and the American College of Medical Genetics recommend that carrier screening for TSD be offered to individuals of Eastern European (Ashkenazi) Jewish, French Canadian and/or Cajun ancestry before or during pregnancy.
Enzyme analysis is the gold standard for TSD carrier screening, and is most often ordered in conjunction with mutation analysis. It is also used to confirm a diagnosis of TSD in an affected individual. Enzyme analysis is performed by measuring hexosaminidase A activity in serum and leukocytes. Hexosaminidase A is present in all tissues and is comprised of two subunits, Hex A and Hex B. Hexosaminidase A% activity is measured (using a fluorescent synthetic substrate) by comparing total activity to heat inactivatable (i.e., hex A) activity. This assay alone can detect approximately 98% of Tay-Sachs carriers regardless of ethnicity. False positives may occur due to pseudodeficiency alleles, improper specimen handling and in females' serum samples due to pregnancy or oral contraceptive use. This test can also detect carriers for Sandhoff disease who most often have a characteristic high Hex A% activity and low total Hex A activity.
Two 5-10 ml ACD (yellow top) tubes are preferred. Sodium (or Lithium) heparin (green top) tubes or EDTA (purple top) tubes are also acceptable.
Ship whole blood at room temperature. Blood samples must be received within 72 hrs of collection. If the sample cannot be sent immediately, separate and freeze plasma (serum) and leukocyte pellets until shipment and ship frozen on dry ice.
Turnaround Time: 10-14 days
CPT Codes: 80500, 83080x4, 82657x4, 84155
Consent and requisition forms: Carrier Screening Requisition and Consent [PDF]
Additional information: Expanded Ashkenazi Jewish Carrier Screening brochure [PDF]