Genetic Disorders


 

Ashkenazi Jewish Disorders

Providing support through education and genetic counseling is central to the mission of the Center for Jewish Genetics. From the knowledge gained through carrier screening, individuals are better prepared to make informed decisions for themselves and their future family.

The Center currently screens for 19 disorders found most frequently in Ashkenazi Jews of Central and Eastern European descent Jews. Many of these disorders are serious and can be debilitating and life-shortening, but with proper knowledge and genetic counseling, they can be prevented.

In addition to the 19 disorders linked to Ashkenazi heritage, the Center’s screening panel includes more than 60 common genetic disorders, including Fragile X. Our genetic counselor is available at every step of the screening process to make sure that all of your questions and concerns are addressed.

This screening process is called carrier screening. Carriers are healthy adults who have the genetic mutation that can potentially be passed on to a child if both parents are carriers for the same gene. This video explains how healthy carrier parents may have a child with the disorder.

Watch this  Youtube Video to learn more about Autosomal Recessive Inheritance

Blooms Syndrome:
Bloom’s syndrome is caused by changes in a gene, BLM, which is responsible for copying and repairing DNA in cells. These changes result in a high incidence of breaks in an individual’s chromosomes. The most serious manifestations of this condition are a predisposition to cancer and a compromised immune system, though there are other significant symptoms as well.

Extra Resources:

Canavan Disease:
Canavan disease is caused by a deficiency of an enzyme called aspartoacylase (ASA). This enzyme helps breakdown a substance in the brain called N-acetylaspartic acid (NAA). NAA, when not broken down properly, interferes with the production of myelin, which is a fatty substance that acts as a protective covering of nerve cells in the brain. Additionally, when the body doesn’t produce the ASA enzyme, the resulting buildup of NAA destroys existing myelin, damaging the brain cells. Most children with Canavan disease appear normal at birth, but exhibit progressive deterioration of physical and mental capabilities in the first few months of life.

Extra Resources: 

Cystic Fibrosis:
Cystic fibrosis (CF) is a progressive multi-system disorder caused by abnormal function of the CFTR protein, which causes the body to produce thick, sticky mucus in the lungs and digestive system. CF is no more common among Ashkenazi Jews than among other Caucasians, and is in fact one of the most common genetic disorders among Jews and non-Jews alike.

Extra Resources: 

Familial Dysautonomia:
Individuals with familial dysautonomia (FD) lack a protein involved in the development and maintenance of the sensory and autonomic nervous systems. This disorder affects basic bodily functions such as swallowing, temperature regulation, blood pressure, sensitivity to heat and pain, stress response and tearing of the eyes. FD is seen almost exclusively in Ashkenazi Jews and is associated with poor development, progressive degeneration and a high mortality rate.

Extra Resources: 

Familial Hyperinsulinism:
Gene mutations that cause familial hyperinsulinism lead to over-secretion of insulin from beta cells in the pancreas, resulting in severe low blood sugar, or hypoglycemia. Unlike typical episodes of hypoglycemia, which occur after periods without food, episodes of hypoglycemia in people with familial hyperinsulinism can also occur after eating or exercising. Insufficient blood glucose deprives the brain of its primary source of fuel. If left untreated, it can lead to irreversible neurological damage or death. 

Extra Resources: 

Faconi Anemia, Group C:
Fanconi anemia is caused by changes that are responsible for copying and repairing DNA in cells. These changes result in a high incidence of breaks in an individual’s chromosomes. Fanconi anemia is characterized by reduced production of all types of blood cells in the body. While many serious problems are associated with this disorder, the most difficult is an increased risk for cancer.

There are various forms of Fanconi anemia that can occur in individuals from any ethnic background. There are at least 15 genes currently known to cause this disorder—one specific form, Fanconi anemia group C, is the most common found in Ashkenazi Jews. Another form, group D1, is caused by mutations in the  BRCA2 gene.

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Gaucher Disease, Type 1:
An enzyme called glucocerebrosidase is necessary for breaking down a specific fatty substance in the body. Lack of this enzyme, caused by a mutation in the GBA gene, causes this fatty substance to accumulate in the bone marrow, spleen, liver and other parts of the body. This can result in anemia, low platelet count, easy bruising and bleeding, bone pain and bone fractures, even with little trauma. There are three different types of Gaucher disease, but type 1 is the most common form in Ashkenazi Jews.

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Glycogen Storage Disease, Type 1A:
Glycogen is a carbohydrate that serves as one of the primary fuel reserves for the body’s energy needs. Stores of glycogen power the body during times of fasting and exercise. Glycogen storage disease type I (GSD I) is caused by an enzyme deficiency that prevents the body from completely breaking down the stored glycogen into glucose, which the body metabolizes. There are two main subtypes of GSD I, caused by mutations in two different genes. GSD Is is the most common subtype in Caucasians, with a relatively high carrier frequency in Ashkenazi Jews.

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Joubert Syndrome:
There are several types of Joubert syndrome, caused by mutations in different genes. Joubert syndrome 2 is most common in Ashkenazi Jews. It is a rare neurological disorder characterized by multiple brain abnormalities, including the absence or underdevelopment of the cerebellar vermis—an area of the brain that controls balance and coordination. 

Extra Resources: 

Maple Syrup Urine Disease:
Maple syrup urine disease (MSUD) is named for the characteristic sweet smell of the urine in affected children. It is caused by genetic mutations that prevent the body from breaking down three specific amino acids in the body. These products then build up to toxic levels, leading to manifestations of the disease. MSUD is caused by mutations in four different genes. There are several forms of this disease, and the classic, severe form is most common in Ashkenazi Jews. (MSUD 1B)

Dihydrolipoamide dehydrogenase deficiency (DLD) is a type of MSUD caused by a mutation in the DLD gene. Although the actual disease is extremely rare, it has a high carrier frequency in the Ashkenazi population—1 in 96.

Extra Resources: 

Mucolipidosis IV (MLIV):
Mucolipidosis IV (MLIV) was first described in 1974. It is part of a group known as genetic lysosomal storage diseases, in which cells can’t produce an enzyme which allows them to break down certain compounds. These compounds then build up and impair cell functions. MLIV is a disease which affects the brain and nervous system.

Extra Resources: 

Nemaline Myopathy:
There are several types of nemaline myopathy, caused by mutations in different genes. It primarily affects skeletal muscles, which are muscles that the body uses for movement. Nemaline myopathy causes muscle weakness throughout the body, but it is typically most severe in the muscles of the face, neck and limbs. This weakness can worsen over time. The muscle problems associated with nemaline myopathy are caused by abnormal buildup of thread-like structures in certain muscle tissue.

Extra Resources: 

Niemann-Pick Disease, Type A:
Your body requires an enzyme called sphingomyelinase to break down a specific type of fat which is key in many neural functions. Individuals with Neimann-Pick type A don’t produce this enzyme, which leads to fat accumulation in various organs of the body, and impairs or inhibits cell functions. Neimann-Pick disease has several subtypes, of which type A is most common in Ashkenazi Jews. While other subtypes of the disease may manufacture enzymes on a very limited scale, individuals with type A produce no sphingomyelinase.

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Spinal Muscular Atrophy:
Spinal muscular atrophy (SMA) causes degeneration of motor neurons, the nerve cells in an era of the spinal cord known as the anterior horn. When the motor neurons break down, so does the link between the brain and the voluntary muscles—those which we control. As the link between the brain, spinal cord and muscles breaks down, the muscles that are used for activities such as crawling, walking, sitting up and moving the head are used less and less and become weaker, or shrink.

Extra Resources:

Tay-Sachs Disease:
Tay-Sachs disease is the most familiar of the Jewish genetic disorders. It is caused by a deficiency of an enzyme called hexosaminidase A, or hex A. This enzyme is needed for the body to break down a fatty waste substance in brain cells. Lack of this enzyme affects the brain and nervous system, causing rapid and progressive deterioration.

Extra Resources: 

Usher Syndrome Type 1F and Type III:
Usher syndrome comprises a group of diseases with a distinctive combination of hearing and progressive vision loss. The genes related to Usher syndrome provide instructions for making proteins that play important roles in normal hearing, balance and vision. They function in the development and maintenance of hair cells, which are sensory cells in the inner ear that help transmit sound and motion signals to the brain. In the retina, these genes are also involved in determining the structure and function of light-sensing cells called rods and cones. Most of the mutations responsible for Usher syndrome lead to a loss of hair cells in the inner ear and a gradual loss of rods and cones in the retina. Degeneration of these sensory cells causes hearing loss, balance problems and vision loss.

Extra Resources:

Walker-Warburg Syndrome:
Walker-Warburg syndrome is a type of congenital muscular dystrophy characterized by brain and eye abnormalities and muscle disease, particularly weakness and atrophy (wasting) of voluntary muscles. The signs and symptoms of Walker-Warburg syndrome are present at birth or in early infancy. Mutations in different genes lead to different forms of WWS, and the forms vary in regard to muscles involved, ages of onset and severity.

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Learn more about the Center's carrier screening and education program.

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We are proud to announce that our Carrier Screening Program is open with our new medical provider Insight Medical Genetics (IMG). Visit our Get Screened page to learn more about our program and how to register!





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Do You Know What's In Your Genes?

What is the most valuable gift you can give to your family? The gift of good health! There are many health conditions that run in families. Knowing your family health history can alert you to the potential risk for a variety of genetic disorders . Be sure to check with your relatives for warning signs and assess your risk for hereditary cancers!

Did you know: Ashkenazi Jews are 10 TIMES more likely to have BRCA mutations, which significantly increases lifetime risks for hereditary cancers, so what does this heightened risk mean for you? Click here to learn more !