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Leading the Fight to treat and cure
Tay-Sachs, Canavan, Sandhoff, GM1 and related diseases

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There are two main types of carrier screening tests: Molecular (analyzing the DNA-genetic code) and biochemical (measuring enzyme activity). Carrier screening for Tay-Sachs disease and Sandhoff disease involves a combination of both genetic and enzyme screening for the most sensitive results.
 

Biochemical / Enzyme Screening:

Enzyme screening is performed using an assay which detects the level of specific enzymes in the blood or a tissue sample. Enzyme assays can be done using serum or leukocytes isolated from blood. For Tay-Sachs disease, screening using serum is the standard of care, but leukocyte screening is recommended when the person being screened is pregnant, on birth control pills, or taking any medications that affect hormones.

The following diseases utilize enzyme screening as the gold standard for carrier screening. Molecular genetic screening should also be performed, as some carriers can be missed via enzyme screening.

Molecular /Genetic Screening:

There are two types of molecular screening:

Most molecular screening only looks for several DNA mutations (changes in genetic code) that lead to decreased production of enzyme. This type of screening often focuses on the mutations seen in one ethnic group and misses those seen in people of other backgrounds. For instance, for Tay-Sachs disease, most molecular screening detects >90% of carriers of Jewish background but only 60% of the mutations found in people of other backgrounds.

The second type of molecular screening is called sequencing. This type of genetic carrier screening is accomplished by reading across the DNA code of a specific gene to determine if there are any known mutations (changes in the DNA code). A negative result significantly reduces the chance that you are a carrier, but it does not eliminate the chance, as it is possible that you carry a mutation that has not been discovered yet or that our current technology is unable to detect. It is important to talk with a genetics professional about how your screening results may impact your family’s health.  

The following allied diseases utilize molecular screening as the gold standard for carrier screening:

     

 

 

People with Ashkenazi (Eastern European) Jewish ancestry are more likely to be carriers of certain genetic conditions. Interested couples can have carrier screening to learn about their chance of having a child affected by one of these diseases. Carrier screening can be used to test for one specific disease or several genetic conditions. The expanded screening is often referred to as the "Jewish Screening Panel". Be sure to confirm which genetic diseases are covered on your screening panel with your ordering genetics provider. Also note that both enzyme screening and molecular screening should be performed for the most sensitive Tay-Sachs disease screening.

If you have any Ashkenazi Jewish ancestry it is important to be screened, even if your partner is not Jewish. While these diseases are more common in people of Jewish ancestry, they can affect the children of couples from many backgrounds, as people of other backgrounds can also be carriers.

What are the diseases that occur more frequently in people of Ashkenazi Jewish descent?

Table Adapted from: The Jewish Genetic Disease Consortium

Published recommendations and resources:

ACOG Committee Opinion - American College of Obstetricians and Gynecologists
ACMG - American College of Medical Genetics
NTSAD Position Statement - Tay-Sachs Carrier Screening

 

Tay-Sachs disease most often affects families with no known history of the disease. A mutation in the HEXA gene can be carried silently through many generations. Carrier screening enables prospective parents to understand the risk of passing on an inherited genetic condition such as Tay-Sachs disease to their children. Carrier screening prior to pregnancy is most advantageous, as it enables a couple to do research, seek resources, and make an informed decision while having the greatest number of reproductive options.

Tay-Sachs disease carriers are more frequently from Ashkenazi Jewish, French Canadian, Pennsylvania Dutch, Irish, and Cajun backgrounds. However, anyone can be a carrier. Be sure to discuss your ancestry with your genetics provider so that appropriate carrier screening is ordered.

Genetic counseling is strongly recommended prior to carrier screening. A genetic counselor can explain testing options, interpret test results, facilitate decision making, and assist with insurance coverage. For more information about how to contact a genetic counselor, visit the Genetic Counseling tab.

 

Enzyme Screening:

Enzyme screening is currently the gold standard for Tay-Sachs disease carrier screening. It is performed using an enzyme assay which detects the level of protein produced in the blood from the HEXA gene for Tay-Sachs. Enzyme assays can be performed using serum or leukocytes isolated from blood. Serum is most commonly used but leukocyte screening is recommended when the person screened is pregnant, taking birth control pills, or on any medications that affect hormones.

The enzyme measured in Tay-Sachs disease screening is called Hexosaminidase A. Individuals with infantile onset Tay-Sachs are expected to have absent or nearly absent Hexosaminidase A enzyme activity while those with juvenile or adult onset Tay-Sachs disease tend to have 6-15% Hexosaminidase A enzyme activity.

 

Molecular Genetic Screening:

Genetic carrier screening for Tay-Sachs disease can also be performed by reading across both copies of one’s HEXA genes and detecting if there are any known changes (mutations). A negative (normal) result significantly reduces the chance of being a carrier, but it does not eliminate the chance. It is possible to carry a mutation that has not yet been discovered or that our current technology is unable to detect.   It is also possible to receive an “uncertain” result called a “variant of uncertain significance” (VUS). This means that a change was found in the spelling of the HEXA gene but it is not yet known if that change is normal human variation or if it denotes carrier status. It is important to discuss how a VUS result may impact your family’s health with a genetic professional.  

 

NOTE: A combination of genetic and enzyme testing is strongly recommended for Tay-Sachs screening for the most sensitive results. View the NTSAD Position Statement on Tay-Sachs Screening

 

General Topics

My partner isn’t Ashkenazi Jewish. Should we still have carrier screening?

Yes! Anybody could be a carrier. Even if your partner is not Jewish it is still possible that you are both carriers for the same recessive condition. Discuss screening options with your doctor or genetics professional (geneticist or genetic counselor) to determine the best screening method for you and your partner.

I’ve heard carrier screening can be done at home. Is that true?

It’s important for you to speak with a genetics professional prior to having carrier screening. Through some programs, a saliva sample can be collected at home and sent to a laboratory for analysis. Saliva testing does not include Tay-Sachs enzyme analysis, but may provide sequencing of multiple genes.

For more information, visit the Screening Centers page.

If I already have a healthy child, do I still need to have carrier screening?

Yes. If you and your partner are carriers for the same recessive disease, there is a 25% chance with each pregnancy that your child will be affected with the disease as well as a 75% chance of having an unaffected child. Two carrier parents could have several healthy children before having an affected child.

Where can I get carrier screening?

It is best to talk with your doctor or make an appointment with your genetics professional to discuss your interest in carrier screening. Each of these medical professionals can explain the screening, submit an order, and interpret the results for you.

For locations, visit the Screening Centers page.

Tay-Sachs Disease

I’m concerned that I may be a carrier for Tay-Sachs disease. What type of carrier screening will offer the most accurate results?

A combination of DNA and enzyme testing is strongly recommended for Tay-Sachs screening for the highest level of detection. Most labs only offer DNA testing for Tay-Sachs. Be sure to request a laboratory that performs both DNA and enzyme testing.

It is also important that your genetic screening is tailored to you and your family history. For example, individuals of Ashkenazi Jewish ancestry are known to have different mutations than individuals from the French Canadian population. It’s important to make sure that you do carrier screening specific to your ancestry.

Some labs offer expanded panels with many conditions aimed at couples with mixed or unknown ancestry. Discuss your interest in carrier screening with your genetics professional and determine which testing is best suited for you.

For more information, visit the Types of Screening page.

Only one of my grandparents is Jewish. Do I still need carrier screening for Tay-Sachs disease?

Yes, it’s important to remember that anyone could be a carrier for Tay-Sachs disease. You are at risk of being a carrier of a Jewish mutation based on your Jewish ancestry. Individuals of Irish, Cajun, French Canadian, and Pennsylvania Dutch descent are also at increased risk of having a Tay-Sachs disease mutation. It may be a good idea for you to have an expanded panel that includes screening for other recessive conditions. Discuss your options with your genetics professional prior to testing.

I’m pregnant and I just found out that I have a family history of Tay-Sachs disease. Can I get carrier screening while I’m pregnant?

Yes, you can get carrier screening for Tay-Sachs disease while pregnant. When women are pregnant or taking birth control pills, detection is best using leukocytes. Make sure that the genetics professional ordering your carrier screening knows that you are pregnant so that the correct testing is ordered. The father of the pregnancy can also pursue carrier screening to determine if he is a carrier. If the father is not found to be a carrier, your baby is at very low risk for Tay-Sachs disease. If he is carrier, you can consider doing an amniocentesis or CVS. These are diagnostic tests that will be able to tell you if your current pregnancy is affected with Tay-Sachs disease or is unaffected. Speak with your obstetrician or genetics professional about this testing.

For more information, visit Family Planning.

I have a “pseudodeficiency allele”. What does this mean?

A “pseudodeficiency allele” reduces enzyme activity but does not cause a disease. A pseudodeficiency allele does not cause Tay-Sachs disease in a carrier or in the children who inherit the pseudodeficiency allele. Even if a person has one Tay-Sachs mutation and one pseudodeficiency allele, they will not develop Tay-Sachs disease. Approximately 30% of non-Ashkenazi Jewish and 3% of Ashkenazi Jewish individuals who are identified as carriers by enzyme analysis have a benign pseudodeficiency allele.

My enzyme carrier screening for Tay-Sachs disease came back as inconclusive. My provider wants me to have genetic testing for Tay-Sachs disease. Is it possible that I’m not a carrier?

Yes. Tay-Sachs disease enzyme analysis is very sensitive but can be affected by pregnancy status, medications, and transport temperature. DNA mutation analysis may help clarify whether an individual is truly a carrier for Tay-Sachs disease. Typically DNA and enzyme testing are performed at the same time to allow for optimal interpretation of results.

A genetics professional can help you to understand what this result means for you and your family. Visit Genetic Counseling to get in contact with a provider near you.

 

Genetic Testing Terminology

What does “gene sequencing” mean?

If you think of a gene as a page in a book, “gene sequencing” refers to reading across each letter of that page to see if there are any “spelling mistakes” in the genetic code. Gene sequencing would detect if “cat” in the book is misspelled as “ctt”. Some coding changes are normal and make us unique individuals. Other coding differences can result in disease.

My doctor told me that I have a “variant of uncertain significance.” What does that mean?

A “variant of uncertain significance” or VUS is a coding change in your genes that has not been seen in enough people to thoroughly understand. We all have genetic variants that make us unique individuals. Some “variants” in your genes are normal and do not affect your health. It is also possible that a variant will eventually explain a disease in your family or increases your chance of having a child with a genetic disease.

Researchers are working to classify these variants and clarify what they mean for your family’s health. Most often a variant of uncertain significance is eventually determined to be “benign” or normal. It is a good idea to check-in with your genetics professional every few years to see if there are updates on your specific variant.

Known Carrier of Tay-Sachs Disease

If I am a carrier for Tay-Sachs disease or an allied disease, does that mean that I will get the disease?

No. Carriers do not express the symptoms of the disease. You need two mutated copies of a particular gene, one inherited from each parent, to develop an autosomal recessive disease.

For more information about autosomal recessive inheritance, visit the About Inheritance page.

I am a carrier for Tay-Sachs disease. Can I test my kids to see if they are also carriers?

Carrier screening is not recommended for children under the age of 18, as it is not helpful in the medical care of healthy children. Once your children are 18 or older they can decide if they would like to pursue carrier screening, prior to considering reproductive options.

My partner and I are both carriers for Tay-Sachs. We do not feel that we could handle the emotional burden of having a baby with Tay-Sachs disease. Is there anything we can do to ensure that we will have a healthy baby?

There are many reproductive options available to increase your chance of a having a healthy baby, specifically a baby that does not have Tay-Sachs disease. Some people choose adoption, others use sperm, egg, or embryo donation from non-carriers, some pursue a natural pregnancy with prenatal testing by amniocentesis or CVS, while others consider in vitro fertilization with pre-implantation genetic diagnosis (PGD).

For more information, visit the Family Planning page.

I am a carrier for Tay-Sachs disease and my husband is not. Is it possible for our children to be affected with Tay-Sachs disease?

Both parents need to be carriers for a child to be affected with an autosomal recessive disease like Tay-Sachs. However, there is a 50% chance with each pregnancy that your child will be a carrier (like you) and a 50% chance that your child will inherit two normal copies of the Tay-Sachs gene.

For a graphic explanation, please visit the About Inheritance page.

I am 12 weeks pregnant and I just found out that I’m a carrier for Tay-Sachs disease. What do I do?

Finding out that you are a carrier while pregnant can be anxiety-provoking. Fortunately, you have several options that will help you better understand the risk to your baby.

The father of the pregnancy can pursue carrier screening to determine if he is also a carrier. If the father is not found to be a carrier, your baby is at very low risk for Tay-Sachs disease. If he is carrier, you can consider doing an amniocentesis or CVS. These are diagnostic tests that will be able to tell you if your current pregnancy is affected with Tay-Sachs disease or is unaffected.Speak with your obstetrician or genetics professional about this testing.

For more information, visit the Family Planning page and the About Inheritance page.

More Answers

My relative had a baby with Tay-Sachs. Should I be concerned?

If your relative had a baby with Tay-Sachs disease, he or she is a carrier. If this is a blood relative, you may be at increased risk to be a carrier. It’s a good idea to discuss this family history information with your doctor or genetics professional. Remember, you are only at risk of having a child with Tay-Sachs disease if both you and your partner are carriers.

I’m French Canadian. My biochemical testing came back inconclusive and my sequencing came back normal. What should I do?

Carriers of French Canadian descent are more likely to have a mutation called a deletion; this means that a region of the HEXA gene is missing. If you think of the HEXA gene as a page in a book, screening by sequencing is only looking for single letter typos, but can fail to detect missing paragraphs. If you are French Canadian, ask your doctor or genetics professional to order genetic testing that will be able to find a large deletion, if present.

If I have late onset Tay-Sachs disease (LOTS), could I have a child with infantile or early onset Tay-Sachs disease?

All individuals with Tay-Sachs disease have a mutation in both copies of their HEXA genes. Some individuals with late onset Tay-Sachs disease have one late onset mutation and one infantile onset mutation. Others have two late onset mutations. If you have one infantile onset mutation and your partner does too, there is a 25% chance with each pregnancy that your child will have infantile or juvenile Tay-Sachs. If you have two late onset mutations and your partner is a carrier for late onset Tay-Sachs disease, your children are at risk for LOTS, but not early onset disease.

See the About Inheritance page for more information about autosomal recessive inheritance.

How can I be screened for genetic diseases?

Your primary doctor or OB/GYN may order the tests but it is strongly recommended to see a genetics professional* to discuss the most current information available. Depending on your health insurance, you may need a referral or you can go directly to a genetic counselor in your network to discuss screening.

Published opinions and recommendations:
ACOG Committee Opinion - American College of Obstetricians and Gynecologists
ACMG - American College of Medical Genetics
document NTSAD  Position Statement (46 KB) - Tay-Sachs Carrier Screening
NTSAD Carrier Screening - Public Service Announcement - Video published on YouTube

*Or other genetics professionals such as a genetic counselor or geneticist.

Can genetic diseases be prevented?

Until a cure is found education, awareness and prevention are the only ways to avoid heartache and loss. EVERYONE, regardless of heritage, should speak with their doctor about genetic counseling and their risk before getting pregnant. 

Carrier Screening

Types of Screening
Jewish Diseases
Tay-Sachs
Prenatal

Screening Centers

Insurance

Education Programs

Family Planning

Genetic Counseling

Ensuring Quality Results

We are all carriers of recessive genetic diseases but standard healthcare practice does not screen everyone for all diseases because the technology does yet exist to accurately and cost effectively screen everyone. Your doctor and / or genetic counselor can help determine based on your family history and heritage which diseases you are at risk to carry.

It is highly recommended to pursue carrier screening before pregnancy because the hormones can reduce the test accuracy.

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