Carrier Testing for Ashkenazi Jewish Genetic diseases: Answers for Health Professionals

Tay-Sachs disease, Canavan disease, familial dysautonomia, Niemann-Pick (type A) disease, Fanconi anemia (group C), Bloom syndrome, Gaucher disease (the non-neuronopathic type), mucolipidosis type IV, and glycogen storage disease type 1.  These are all uncommon conditions that are predominantly found in persons of Ashkenazi ancestry.  [Tay-Sachs disease is also found in persons of French-Canadian (Acadian) ancestry and, rarely, in mixed Jewish/non Jewish couples.]  Although not strictly a disorder of European Jews, cystic fibrosis is often included in an Ashkenazi heritage screening panel, since it occurs with the same frequency in European Jews as in members of the non-Jewish Caucasian population (approximately 1/3,000).

All are autosomal recessive, which means both members of a couple must be carriers in order to have an affected child, in which case the risk of an affected child is 25% for each pregnancy.  In the United States, carriers of Tay-Sachs disease, Canavan disease, familial dysautonomia, Fanconi anemia type C, Bloom syndrome, Niemann-Pick type A, and mucolipidosis type IV are predominantly of European-Jewish ancestry.  Carrier frequencies in Ashkenazi Jews range from 1/30 (for Tay-Sachs disease) to 1/100 (for Bloom syndrome).  Except for cystic fibrosis, for which the carrier frequency in Jews and non-Jewish Caucasians is equal, the carrier frequency for non-Jews is probably 10 fold lower.

Tay-Sachs, Canavan, and Niemann-Pick disease all present as neurodegenerative disorders.  The onset is usually in infancy or childhood, and most affected individuals ultimately reach a vegetative state prior to demise.  Growth and development is typically normal until signs of neurodegeneration develop.  Individuals with Bloom syndrome and Fanconi anemia have growth problems and have a predisposition to early death from cancer.  Fanconi anemia, unlike Bloom syndrome, also involves cognitive impairment, and Bloom syndrome patients have immune deficiency.  Familial dysautonomia can be very difficult to diagnose and may result in sudden death in infancy or childhood before being diagnosed.  The main problems in familial dysautonomia include abnormal temperature and blood pressure regulation, abnormal sweating, insensitivity to pain, and feeding difficulties in infancy.  The non-neuronopathic type of Gaucher disease often results in anemia, hepatosplenomegaly, and bony lesions in adults.  However, no neurologic or cognitive impairment is present.  Gaucher disease can often be asymptomatic or minimally symptomatic.  Carrier screening for Gaucher disease has identified affected individuals with no apparent symptoms of the disease.  Of all these conditions, only Gaucher disease is treatable.

Except for non-neuronopathic Gaucher disease, all are serious and untreatable, or only partially treatable.  In particular, infants with Tay-Sachs and Canavan disease progress normally for the first several months, only to begin inexorable neurologic deterioration.  Obviously, this is devastating to the families of affected children.

Sensitive carrier screening by molecular analysis for multiple disorders can be easily accomplished on a single small blood sample.  Tay-Sachs carrier testing by enzyme analysis is 97-99% sensitive and is 94% sensitive by molecular analysis.  Molecular testing for the other conditions has a sensitivity exceeding 95% in persons of Ashkenazi Jewish heritage.  Thus, even if one member of a Jewish couple is discovered to be a carrier, negative results on the other makes having an affected baby exceedingly unlikely.

Cystic fibrosis carrier testing should be offered to all Caucasian couples who are pregnant or planning a pregnancy.  Either partner can be tested prior to the first trimester, whereas couple screening may be of benefit when a patient is beyond about 14 weeks gestation.  ACOG recommends "making available" testing to non-Caucasians.  Many states, including New York, mandate that patients be informed prior to being tested and give consent for this testing.

All patients and/or their partners who are both of either European-Jewish or French-Canadian ancestry should be offered Tay-Sachs carrier testing by enzyme based methods (leukocyte or platelet hexosaminidase A in pregnant women or women taking oral contraceptives, and serum hexosaminidase A for non pregnant patients and their partners).  Whether to offer combined (both members of a couple at once) or sequential testing is up to the practitioner and depends on personal preference and how quickly the information is needed for prenatal diagnostic purposes.

Couples who are both of European-Jewish ancestry should be offered, at a minimum, Canavan disease testing as recommended by ACOG.  Testing for familial dysautonomia should also be strongly considered.  A more extensive panel, including any or all of the other diseases described above, can also be offered.  Since Gaucher disease is treatable and substantially less serious than the other conditions, many individuals would not choose to have carrier screening for this condition.

We suggest that mixed (Jewish and non-Jewish) Caucasian couples should be offered cystic fibrosis carrier screening. Enzyme based Tay-Sachs carrier screening may also be offered for either or both members of those couples.  However, your patient should be informed that the chance of having a baby with Tay-Sachs disease when only one member is of European-Jewish ancestry is less than 1/30,000.  If Tay-Sachs screening is desired in mixed couples, all things being equal, it is preferable to test the Jewish individual.  Since molecular analysis for Canavan disease, familial dysautonomia, Niemann-Pick disease, Fanconi anemia, mucolipidosis IV, glycogen storage disease, and Bloom syndrome are only useful in persons of Jewish ancestry, we see no reason to test either member of a mixed couple for these conditions.

New York State requires a written  informed consent for genetic testing be obtained.

Enzyme based Tay-Sachs carrier testing requirements are such that it is often better to refer your patient to the laboratory drawing station than to obtain blood in the office.  Some laboratories reject any non frozen serum samples and cannot transport leukocyte samples to arrive at their testing facility within the required 48 hours.  Molecular based carrier testing for multiple conditions can typically be performed on a single lavender top tube sent to the laboratory at room temperature.

Clinical information necessary for the laboratory to process the sample should be included with the sample or requisition.  The information recommended is summarized in our Jewish genetic testing request and history form.

Patients may benefit from a genetic consultation prior to having carrier screening.  Any patient with a positive family history, intending to have prenatal diagnosis for another indication, or someone who is identified as being a carrier should be offered a genetics referral.

Be prepared for lots of paper from this testing; many laboratories consider each test separate and send several pages of results for each test.

---

Ashkenazi screening information for patients

Services | Insurance | Directions | Glossary | Genetics links | Topics of Interest | Our Staff | Pictures | Contact us | Home

 

© 2001, 2003 The Genetics Center, Inc, All Rights Reserved.                                      October 3, 2001  revised December 12, 2003