Maternity Care Guidelines: Screening for Tay Sachs Carriers

Literature Search:
The MeSH heading *Tay-Sachs Disease AND mass screening.mp. or exp Mass Screening was searched on Medline for the years 1998 to 2005.

Summary of Evidence:
Tay-Sachs disease (TSD) is a lysosomal storage disease causing severe progressive neurological symptoms that primarily affects the Ashkenazi (Eastern European) Jewish population. [1, 2] It is a recessive disorder with a carrier frequency in the Ashkenazi Jewish population of between 1/20 and 1/30. [3] It has been shown that people of French Canadian (particularly Gaspé region) and Cajun descent also have a greater carrier frequency than the general population. [1, 4]

Tay-Sachs disease is characterized by a deficiency in the hexoaminidase A enzyme and exists in two forms: the infantile and juvenile forms. Children stricken with the infantile form die by age 2 to 3 years, while children with juvenile form die by age 15. [2] Due to the mortality and emotional suffering for the parents associated with Tay-Sachs disease, carrier testing for TSD has been carried out for 20 years and has resulted in a 90% decrease in the incidence of TSD. [4]

Carrier testing can be done by measuring serum hexosaminidase A in men or non-pregnant women. If testing is done in women who are pregnant or using oral contraceptives, leukocyte testing must be used instead of serum testing. Prenatal testing for TSD can also be done by measuring hexosaminidase activity in samples obtained by amniocentesis or chorionic villus sampling. [4] Molecular diagnostic testing is now available in some centres. [5] For Ashkenazi Jews, DNA testing is now the preferred method of carrier testing as it identifies 99.9% of carriers. [5] for non-Jewish individuals, initial carrier testing can be done by enzyme assay. Positive or inconclusive results can be confirmed by DNA mutation analysis. [5]

Recommendations of Others:
The Canadian Task Force on Preventive Health Care gives it a grade A recommendation. [6]

The American College of Obstetricians and Gynecologists recommends screening for TSD before pregnancy of both members of a couple who are Ashkenazi Jews or of French Canadian or Cajun descent or have a family history of TSD.[1] When only one member of a couple is from a high risk group, they should be screened first. If a woman is currently pregnant, both partners should be screened simultaneously so that the results are available early enough to ensure that all options are available to the couple. Ambiguous tests should be confirmed by molecular analysis for the most common mutations. If both partners are carriers, genetic counseling and prenatal diagnosis should be offered. [1, 4]

Patients Handouts and background information can be found at:

National Tay-Sachs and Allied Diseases Association (NTSAD):
http://www.ntsad.org/

March of Dimes:
http://www.marchofdimes.com/professionals/681_1227.asp

Medline Plus:
http://www.nlm.nih.gov/medlineplus/taysachsdisease.html

Conclusion:
The new guideline for Tay-Sachs screening on the MCC 2003 should be bolded to read:

Tay Sachs disease testing in Ashkenazi Jews by hexosaminidase-A in serum (men, non-pregnant women) or WBCs (pregnant women).
It will be in bold font as there it is a grade A recommendation
Listed under "Investigations" suggested for preconception visit (or alternatively, early pregnancy)

Reviewers:
Amrit Kahlon, (medical student) - July 2002
Colleen Kirkham MD, CCFP, FCFP - October 2002

Updated by Colleen Kirkham - March 2005

Thank you to Dr. Sylvie Langlois (Department of Medical Genetics, Children's and Women's Health Centre of British Columbia) and Dr. Hilary Vallance (Biochemical Genetics lab, Department of Pathology, Children's and Women's Health Centre of British Columbia) for their helpful comments.

3/30/2005

Anonymous, Screening for Tay-Sachs disease. International Journal of Gynaecology & Obstetrics., 1996. 52(3): p. 311-2.
Hansis, C. and J. Grifo, Tay-Sachs disease and preimplantation genetic diagnosis. Advances in Genetics, 2001. 44: p. 311-5.
Shabat, S., Economics of screening programs for Tay-Sachs disease. Health Policy., 1999. 47(2): p. 183-4.
Kaback, M.M., Population-based genetic screening for reproductive counseling: the Tay-Sachs disease model. European Journal of Pediatrics., 2000. 159(Suppl 3): p. S192-5.
Sutton, V.R., Tay-Sachs disease screening and counseling families at risk for metabolic disease. Obstetrics & Gynecology Clinics of North America., 2002. 29(2): p. 287-96.
Canadian Task Force on the Periodic Health Exam:The Canadian Guide to clinical preventive services. 1994, Ottawa: Health Canada.