Jewish Genetic Diseases
Frequently Asked Questions
The information included here provides answers to some of the most frequently asked questions. If you need additional information, please seek appropriate genetic counseling. [Genetic counseling is the process of providing individuals with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. This section deals with genetic risk assessment and the use of genetic testing to clarify genetic status. It is not meant to address all personal or cultural issues that individuals might face or to substitute for a consultation with a genetics professional.]
- Q. What is genetic testing?
- Q. How do genes cause disease?
- Q. Why do people ask for genetic testing?
- Q. How are genetic diseases passed from one generation to the next?
- Q. What is a "carrier"?
- Q. What information can genetic testing provide?
- Q. Why are both members of the couple tested?
- Q. How is testing performed?
- Q. Which diseases can be detected?
- Q. What does it mean if a person is identified as a carrier?
- Q. How long will it take for the test results to be available?
- Q. How will I be notified of the results?
- Q. What is an enzyme? What is an enzyme deficiency disease?
Brief descriptions of the diseases
- Gaucher disease (GD)
- Cystic fibrosis (CF)
- Tay-Sachs disease (TSD)
- Canavan disease (CD)
- Niemann-Pick disease (NPD)
- Fanconi anemia (FA)
- Genetic testing involves the examination of a person's DNA, the chemical alphabet that "spells out" genes just as letters spell out words. Genes are the blueprints or instructions used to make the body's building blocks or cells. Genetic testing enables doctors to check for defects in the DNA that may cause a disease.
- Every part of your body depends on the instructions contained in one or more genes. Some genes determine characteristics that do not affect your health, such as eye color or the shape of your ears. Others determine critical components that must function correctly in order for your body to be healthy. Genes that spell out a defective component can cause a disease, which in some cases may be handed down through the generations just like eye color.
There are several different reasons why people may request genetic testing. For example:
- A person whose family members have been diagnosed with a genetic disease, such as cystic fibrosis, may want to know if he or she also has the gene that causes the disease.
- A person might be concerned about a genetic disease that is more common in people of their ethnic background. For example, people of eastern European Jewish ancestry (Ashkenazi Jews) have a higher risk of a disorder known as Tay-Sachs disease.
- A person might be suffering from problems that may be due to a genetic disorder. For example, bone pain and anemia (a low number of the red blood cells that carry oxygen in the blood) are symptoms of a disorder known as Gaucher disease, a condition that is diagnosed by genetic testing.
- Every person has two copies of each gene. When a man and a woman have a child, each contributes one copy of their genes to that child. For most genetic diseases, including all the diseases discussed here, the disease occurs only if the child has two copies of the defective gene. That is because one normal, undamaged copy of the gene is enough to tell the body how to correctly build the component that is controlled by that gene. Physicians call this kind of gene an autosomal recessive gene. Autosomal means that it is not associated with the genes that determine whether the baby will be a male or a female. This implies that the risks are equal for boy and girl babies. Recessive means that if even one copy of the gene is normal, the damaged gene "recedes" into the background and cannot cause disease.
- A carrier is a person who has one copy of the defective gene and one copy of the normal gene. Because having even one normal copy of the gene is enough to prevent the disease, this person would not suffer from an autosomal recessive disease if he or she only carries a single copy of the defective gene. However, if the carrier has a child with another carrier, who also has one copy of the defective gene, there is a chance that the baby will have two copies of the defective gene and be affected. For that reason, couples who suspect they could be carriers may decide to undergo genetic testing to find out if they are at risk of having a baby with a genetic disease.
Genetic testing, or DNA testing, can tell a couple whether one or both partners carry a specific autosomal recessive gene defect. If neither is a carrier, or if only one is a carrier, then there is no risk of having a baby with the disease. If, however, both members of the couple are carriers, then there is one chance in four (25%) that a baby would be affected by the disease. (The one-in-four risk is based on the fact that each parent contributes one of his or her two copies of the gene, so the risk of the baby having two defective copies is 1/2 x 1/2 =1/4)
A couple may wish to be tested before deciding to have a baby. Genetic testing can also be performed during pregnancy using procedures referred to as chorionic villus sampling (CVS) or amniocentesis. Pregnancy does not affect the results of genetic testing.
- Even though the child is at risk only if both parents are carriers, physicians usually prefer to test both parents at the same time. This avoids the possibility of a delay in testing if one parent is found to be a carrier. Also, a finding that one member of the couple is a carrier indicates a need for further counseling regarding residual risks.
- The test is performed on a sample of blood, which can be drawn from a vein in the arm or hand at your physician's office. Providing a sample is easy and almost painless.
- There are several disorders that have been called "Jewish genetic diseases" because they are much more common in the Jewish community. You should know, however, that these diseases are not limited to Jewish individuals. They also occur in the non-Jewish community, but they are less frequent.
|Disease Name||How Many Ashkenazi Jews Are Carriers of the Gene Defect?||How Accurate Is the Genetic Test in Detecting Carriers?|
|Gaucher disease||1 in 15||90%-95%|
|Cystic fibrosis||1 in 25||97%|
|Tay-Sachs disease||1 in 30||
97%-98% (enzyme test)
94% (DNA test)
|Canavan disease||1 in 40||98%|
|1 in 90||95%|
|1 in 90||99%|
Note: The estimated frequency at which the disease would occur can be calculated by multiplying the risk of two parents being carriers. For example, for Gaucher disease, the frequency would be 1/15 x 1/15 x 1/4 = 1/820 children.
If you are found to be a carrier, this may affect other members of your family. If you are a carrier, other members of your family may also be carriers, or they may even be at risk of having the disease. To help in understanding the potential meaning of these tests, carriers and their family members should receive genetic counseling. Genetic counseling is available through NYU Medical Center.
Please note that some people may have Gaucher disease and not know about it. Testing for Gaucher disease may reveal that you have the condition. Establishing the diagnosis may lead to careful follow-up, monitoring, or treatment to prevent development of disease complications.
- It may take 2 to 3 weeks for the results to be ready. In a few cases, a repeat sample may be required to verify the results.
If there is a positive result (that is, if a defective gene is found), your physician will inform you of this result by telephone and will review the significance of the findings. This result will be confirmed in writing and will be provided only to you. A normal result will be communicated to you in writing.
Please note that none of the genetic tests performed lead to 100% detection, because there are other, very rare gene defects that may be unique to a single family or a few families. These very rare defects are not routinely checked. The laboratory uses standard techniques, and every effort is made to obtain an accurate, reliable result and minimize the risk of errors.
- Enzymes are natural chemicals in the body that promote essential reactions and processes. Some enzymes break down substances that, if not removed, can build up to dangerous levels. People with two defective copies of the gene for that enzyme may be unable to break down the substance, which then accumulates and causes a disease. Many of the Jewish genetic diseases, including Gaucher disease, Tay-Sachs disease, Canavan disease, and Niemann-Pick disease, are enzyme deficiency diseases
Brief descriptions of the diseases
Please note that each of these diseases may have different effects and a variable impact on quality of life. Of these diseases, only Gaucher disease can currently be treated effectively. However, for the other diseases, supportive care can be provided to relieve suffering or pain.
GD is caused by a deficiency of the enzyme glucocerebrosidase. The absence of this enzyme leads to the accumulation of a fatty material called glucosylceramide. Among the problems caused by the disease are tiredness due to a low number of oxygen-carrying red blood cells (anemia); swelling of the spleen and liver; and painful, brittle, and fractured bones. Most GD patients have what is known as Type 1 disease, in which the brain and nervous system are unaffected. The course of Type 1 disease can vary between individuals; some individuals may have severe problems in early childhood while others may never develop symptoms even late in life. Very rare forms of GD (Types 1 and 2) involve the brain, and patients with these forms of the disease have shortened life-spans. Treatment is available for Type 1 GD.
CF is a condition that may cause breathing difficulties, intestinal problems, infertility, and other medical problems as a result of abnormally thickened body secretions. Most CF patients are identified in childhood, and the disease usually grows worse with time. Although there is no cure for CF, treatments are available to help patients breathe better, reduce the damage caused by repeated lung infections, and help maintain normal nutrition. In recent years, the life expectancy of patients with CF has increased, and more than half now survive into their twenties. CF does not affect intelligence.
TSD is caused by a deficiency of an enzyme known as hexosaminidase A. The absence of this enzyme leads to the accumulation of the toxic material GM2 ganglioside. Problems associated with TSD include difficulty in swallowing, loss of coordination, seizures, and blindness. Classical (infantile) TSD appears early in life, usually between 6 and 8 months of age, and death is inevitable, usually occurring between 3 and 5 years of age. There is a less common form of TSD, known as late-onset GM2 gangliosidosis, that affects adults rather than children. This form of the disease causes slurring of speech, muscle weakness, clumsiness, and gait problems. Patients with late-onset GM2 gangliosidosis have progressive disease with reduced life-span. There is no treatment for TSD.
CD is caused by a deficiency of the enzyme aspartoacylase. The absence of this enzyme leads to the accumulation of N-acetylaspartic acid (NAA). Children with CD have severe delay in development, difficulty in sucking, irritability (which may be expressed as inconsolable crying), and a progressively enlarging head (macrocephaly). These symptoms usually appear before 6 months of age, and the disease worsens steadily. Blindness usually occurs between 6 and 18 months of age. Most patients with CD live only 1 to 3 years, although some have lived to reach 10 years of age. There is no treatment for CD.
NPD is caused by a deficiency of the enzyme acid sphingomyelinase, which leads to accumulation of the fatty material sphingomyelin. Deficiency of this enzyme causes problems that usually appear in the first year of life and include (for NPD type A) failure to thrive, swelling of the liver and spleen, and a rapid mental degeneration. Death occurs within 2 to 3 years. There is no treatment for NPD.
FA is a disease that causes different effects in different patients, including a growing loss of red blood cells, short stature, and birth defects that affect the kidneys and hands. About 25% of children with FA have learning disabilities or mental retardation. FA is also associated with an increased risk of cancer, especially leukemia. The gene defect causing FA type C leads to production of a defective molecule, which may interfere with repair of damaged DNA and control of cell growth. FA is generally fatal unless corrected by bone marrow transplantation.