Hexosaminidase A (Tay-Sachs Disease)
Related Gene(s): HEXA
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 intellectually disabled, paralyzed, and unaware of their surroundings. Onset is typical at approximately 6 months of age, and the 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 the total hexosaminidase activity (Hex A and Hex B) in plasma (serum) or leukocytes using a synthetic flurogenic substrate (4-MUG). The Hex A activity percentage is measured by comparing the heat inactivated activity (Hex A) to the total hexasominidase 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 due to pregnancy or oral contraceptive use in females’ serum samples. This test can also detect carriers for Sandhoff disease who most often have a characteristic high Hex A activity and low total hexosaminidase activity.
Prior to ordering prenatal testing, please contact our laboratory at 800-298-6470. Prenatal testing is available on direct and cultured CVS as well as cultured amniocentesis samples.
Chorionic villus sampling (CVS)
- If cultures are to be established at our laboratory, please submit at least 10 mg of direct CVS specimen
- If cultures are to be established externally, please submit 6-8 mg of direct CVS specimen and three or four T25 cultured flasks for confirmation testing (and two T25 cultured flasks of control specimen)
- If a direct specimen is unavailable, please submit three or four T25 cultured flasks (and two T25 cultured flasks of control specimen)
- If cultures are to be established at our laboratory, please submit at least 15 ml of whole amniotic fluid
- If cultures are to be established externally, please submit three or four T25 cultured flasks (and two T25 cultured flasks of control specimen)
Additionally, please send:
- Maternal blood: 5-10 mL in EDTA tube (lavender top) required to perform MCC studies on all prenatal samples and in case maternal confirmation studies are necessary
- Paternal blood: 5-10 mL in EDTA tube (lavender top) in case paternal confirmation studies are necessary
- Anticoagulated blood: 5-10 mL in ACD tube (yellow top) is preferred. Sodium (or lithium) heparin tubes (green top) or EDTA tubes (lavender top) are also accepted
- Ship at room temperature. Sample must be received within 72 hours of collection
- If the sample cannot be sent within 72 hours, centrifuge immediately and freeze plasma and leukocyte pellets. Then ship frozen on dry ice
- 7-10 days