What You Need To Know About Ashkenazi Genetic Diseases

The numbers are frightening: 1 in 4 Ashkenazi Jews is a carrier for at least one genetic disease. The genetic mutations responsible for these diseases have been passed on from a very small original population — our ancestors who migrated from the Middle East to Eastern Europe around 70 C.E. This is called the founder’s effect. Because Jews tended to marry among themselves, the gene pool remained homogenous and the mutations continued to be inherited.

These mutations are mostly recessive, meaning that mutations must be present in both copies (alleles) of the gene for the associated condition to be expressed. When both parents carry a given mutation, each child of theirs has a 25% of developing the associated disease. This is why couples among whom at least one partner has one or more Ashkenazi Jewish grandparents are urged to undergo genetic screening before conceiving children.

Most labs offer panels that screen for the 19 most common disease carriers, and many insurance companies cover the cost of testing. Some providers offer saliva screenings, though blood tests are more common, and carriers for some diseases — like Tay-Sachs — can only be reliably detected using blood samples.

The Forward Staff has put together a guide to the 19 most common heritable “Ashkenazi Jewish diseases” along with information on symptoms, causes and carrier and detection frequency for each. We’ve also listed support groups in the United States.

Not included on this list are some mutations that are not typically screened for before pregnancy, such as those of the BRCA genes. Because each individual might be at risk for different mutations due to familial risk factors, personal genetic counseling is recommended in conjunction with screening.

Data on the estimated carrier rate are courtesy of the Yeshiva University Program for Jewish Genetic Health in New York. Data on the disease incidence are taken from the the paper ‘Carrier testing for Ashkenazi Jewish disorders in the prenatal setting: navigating the genetic maze’ published in the American Journal of Obstetrics and Gynecology in February 2014.

Dr. Adele Schneider, the medical director of the Einstein Victor Center for the Prevention of Jewish Genetic Diseases in Philadelphia, Pennsylvania, has contributed to this section.

  1. Bloom Syndrome

    Estimated Carrier Frequency
    1 in 100

    Disease Incidence 1 in 40,000

    Symptoms
    It is characterized by poor growth, sun sensitive skin rash on the face, immune dysfunction, childhood leukemia and a predisposition to various cancers.

    Causes
    Mutations in the BLM gene cause chromosome instability. Cancer results from genetic changes that allow cells to divide in an uncontrolled way.

    Treatment
    No cure is available, but chemotherapy for cancers and antibiotics for infections can be given.

    Contact
    Bloom’s Syndrome Foundation
    7095 Hollywood Boulevard #583
    Los Angeles, CA 90028

  2. Bloom Syndrome

    Estimated Carrier Frequency
    1 in 100

    Disease Incidence 1 in 40,000

    Symptoms
    It is characterized by poor growth, sun sensitive skin rash on the face, immune dysfunction, childhood leukemia and a predisposition to various cancers.

    Causes
    Mutations in the BLM gene cause chromosome instability. Cancer results from genetic changes that allow cells to divide in an uncontrolled way.

    Treatment
    No cure is available, but chemotherapy for cancers and antibiotics for infections can be given.

    Contact
    Bloom’s Syndrome Foundation
    7095 Hollywood Boulevard #583
    Los Angeles, CA 90028

  3. Bloom Syndrome

    Estimated Carrier Frequency
    1 in 100

    Disease Incidence 1 in 40,000

    Symptoms
    It is characterized by poor growth, sun sensitive skin rash on the face, immune dysfunction, childhood leukemia and a predisposition to various cancers.

    Causes
    Mutations in the BLM gene cause chromosome instability. Cancer results from genetic changes that allow cells to divide in an uncontrolled way.

    Treatment
    No cure is available, but chemotherapy for cancers and antibiotics for infections can be given.

    Contact
    Bloom’s Syndrome Foundation
    7095 Hollywood Boulevard #583
    Los Angeles, CA 90028

  4. Canavan Disease

    Estimated Carrier Frequency
    1 in 57

    Disease Incidence 1 in 6,400

    Symptoms
    Normal development for the first 3 to 5 months is followed by the loss of skills and progressive neurological decline. Affected individuals develop a large head and seizures. Lifespan limited but may be into teenage years.

    Causes
    Mutations in the ASPA gene lead to deficiency of an enzyme called aspartoacylase. This prevents the breakdown of the compound NAA, which in turn damages myelin, the protective layer around nerve cells. Without myelin, nerve cells die and brain damage occurs.

    Treatment
    No cure is available, but medications can reduce seizures. Gene therapy research is underway.

    Contact
    Canavan Foundation
    450 West End Avenue #6A
    New York, NY 10024
    (866) 907-1847

  5. Cystic Fibrosis

    Estimated Carrier Frequency
    1 in 26

    Disease Incidence 1 in 2,500-3,000

    Symptoms
    The body produces abnormally thick, sticky mucus in the lungs and digestive system. The disorder is characterized by chronic cough or upper respiratory infection, poor weight gain, chronic diarrhea or gastrointestinal problems, failure to thrive, and elevated sweat electrolyte levels. More than 95% of males with CF have reduced fertility. Fertility in females may be decreased as well. The average life expectancy today is 37 years.

    Causes
    Mutations in the CFTR gene lead to abnormal transfer of salt across cell membranes, especially in the cells of the lungs and digestive tract. This causes the body to produce thick, sticky mucus that clogs the lungs and impairs organ function.

    Treatment
    No cure is available but treatment of CF has improved dramatically. Antibiotics can reduce or treat infection, and medication to decrease thick mucus is given. Pancreatic enzymes can help alleviate GI symptoms. Lung transplant may be needed.

    Contact
    The Cystic Fibrosis Foundation
    6931 Arlington Road, 2nd floor
    Bethesda, Maryland 20814
    (800) FIGHT CF (344-4823)

  6. Dihydrolipoamide Dehydrogenase Deficiency (DLD)

    Estimated Carrier Frequency
    1 in 96

    Disease Incidence 1 in 45,796

    Symptoms
    Also known as maple syrup urine disease type 3, it presents in early infancy with recurrent episodes of vomiting and abdominal pain, seizures, hypoglycemia (low blood sugar) as well as poor feeding, lethargy, low muscle tone and developmental delays. A milder form has been described where illness or fasting results in symptoms that respond to treatment.

    Causes
    The cause is a mutation in the DLD gene, which makes a protein necessary for enzymes that produce energy in cells. The flaw leads to amino acids building up to toxic levels in the body.

    Treatment
    Dietary intervention can slow down the progression and reduce symptoms.

    Contact
    MSUD Family Support Group
    Holmes Morton, M.D. Clinic for Special Children
    P.O. Box 128
    Strasburg, PA
    (717) 687-9407

  7. Familial Dysautonomia

    Estimated Carrier Frequency
    1 in 30

    Disease Incidence 1 in 3,600

    Symptoms
    It is a disorder of the sensory and autonomic nervous systems. The hallmark of FD is the lack of overflow tears with crying. Individuals with FD may have difficulty feeding in infancy and show decreased pain sensitivity. They have frequent infections and some have learning disabilities. Individuals with FD often have autonomic crises, in which they cannot regulate their blood pressure, heart rate and temperature. These can occur at any time and may require hospitalization.

    Causes
    It is caused by mutations in the IKBKAP gene, which lead to abnormal production of the IKAP protein. This protein is found in a variety of cells throughout the body, including brain cells, and it is necessary for proper development and maintenance of the sensory and autonomic nervous systems.

    Treatment
    No cure is available, but symptoms can be managed. Patients are frequently hospitalized.

    Contact
    Familial Dysautonomia Now Foundation
    1170 Green Knolls Drive
    Buffalo Grove, IL 60089
    (847) 913-0455

  8. Familial Hyperinsulinism (FHI)

    Estimated Carrier Frequency
    1 in 66

    Disease Incidence 1 in 18,496

    Symptoms
    The disease is characterized by the overproduction of insulin by the pancreas, which results in low blood sugar (hypoglycemia). This can vary from mild to severe. Hypoglycemia can be present in the immediate newborn period through the first year of life and cause symptoms such as seizures, poor muscle tone, poor feeding and sleep disorders if it is left untreated.

    Causes
    In the Ashkenazi Jewish population, two founder mutations in the ABCC8 gene are responsible for approximately 97% of FHI. ABCC8 encodes a protein that functions as a modulator of insulin release. When it is mutated there is increased insulin release from the pancreas resulting in low blood sugar.

    Treatment
    Medication can be given to increase blood sugar. Parts of the pancreas might be removed. If left untreated, FHI can result in irreversible brain damage.

  9. Fanconi Anemia Type C

    Estimated Carrier Frequency
    1 in 89

    Disease Incidence 1 in 32,000

    Symptoms
    Most affected individuals have impaired bone marrow function with a reduced number of all types of blood cells in the body, leading to anemia and bone marrow failure, usually in the first decade of life Infants may be born with malformations of thumbs and kidneys and have abnormal skin pigmentation. There is a high risk of developing cancer or leukemia.

    Causes
    Fanconi anemia is considered a “chromosome breakage” disease. This means that individuals affected with this disease have an increased rate of breakage and rearrangements along their chromosomes. A single mutation in the FANCC gene is unique to FA patients of Ashkenazi Jewish ancestry.

    Treatment
    Transfusions can be given for low cell counts. Therapy with steroids and bone marrow transplantation may be helpful to treat the anemia or bone marrow failure.

    Contact
    Fanconi Anemia Research Fund 1801
    Willamette Street, Suite 200
    Eugene, OR 97401
    (541) 687-4658
    (888) FANCONI

  10. Gaucher Disease

    Estimated Carrier Frequency
    1 in 15

    Disease Incidence 1 in 900

    Symptoms
    Gaucher (pronounced “go-shay”) disease comes in several different forms. Type 1 is the most common in Ashkenazi Jews. Symptoms include enlargement of the liver and spleen, anemia, low platelets (causing easy bruising), nose bleeds and bone pain. The IQ is normal and the age of onset varies.

    Causes
    Mutations in the GBA gene lead to the lack of an enzyme called glucocerebrosidase, which is necessary to break down a fatty substance in cells. As a result, this fatty substance builds up in the liver, spleen, bone marrow and other areas of the body.

    Treatment
    Intravenous and oral enzyme therapies replace the missing enzyme and can reverse some of the symptoms.

    Contact
    National Gaucher Foundation 2227 Idlewood Road, Suite 6
    Tucker, GA 30084
    (877) 649-2742

  11. Glycogen Storage Disease Type 1A

    Estimated Carrier Frequency
    1 in 71

    Disease Incidence 1 in 16,384

    Symptoms
    In this disease the buildup of glycogen in the body’s cells impairs their ability to function normally and can present as hypoglycemia (low blood sugar) in the first few months of life. Hypoglycemia can lead to seizures and glycogen and fat can accumulate in the liver and kidneys. Early diagnosis and treatment have improved prognosis. Normal growth and puberty may be expected in treated children, and many affected individuals live into adulthood.

    Causes
    Mutations in the G6PC gene, which produces proteins to break down glycogen, result in severe hypoglycemia and other signs and symptoms of the GSDI disorders.

    Treatment
    Medical nutritional therapy with frequent day time feeds are needed to maintain normal blood glucose concentrations, prevent hypoglycemia, and provide optimal nutrition for growth and development.

    Contact
    Children’s Fund For Glycogen Storage Disease Research
    917 Bethany Mountain Road
    Cheshire, CT 06410
    (203) 272-CURE

  12. Joubert Syndrome

    Estimated Carrier Frequency
    1 in 92

    Disease Incidence 1 in 33,856

    Symptoms
    The hallmark of Joubert syndrome is the “molar tooth sign,” or an area that looks like the cross-section of a tooth on a brain MRI. Characteristic features of the condition include episodes of unusually fast or slow breathing in infancy and abnormal eye movements. Variable intellectual disability occurs, as well as abnormalities in the retina and kidney disease.

    Causes
    An Ashkenazi founder mutation in the TMEM216 gene causes Joubert syndrome in this population. The gene is expressed in the regions of the body most involved in this syndrome such as the brain, kidneys and limbs.

    Treatment
    There is no cure, but symptoms can be treated individually.

    Contact
    Joubert Syndrome & Related Disorders Foundation
    1415 West Avenue
    Cincinatti OH, 45215
    (614) 864-1362

  13. Maple Syrup Urine Disease (MSUD)

    Estimated Carrier Frequency
    1 in 81

    Disease Incidence 1 in 37,636

    Symptoms
    Maple syrup urine disease is named for the characteristic sweet smell of affected infants’ urine. Infants present with poor feeding and irritability followed by lethargy if untreated. Affected individuals have an intellectual disability, limited or absent speech, difficulty chewing and swallowing, weak muscles and problems controlling hand movements. Vision may be normal at birth but the clouding of the cornea and retinal degeneration lead to vision loss over the first decade of life.

    Causes
    BCKDHB is the gene that causes the disorder in the Ashkenazi population. The BCKDHB gene provides instructions for making part of an enzyme that is responsible for a step in the normal breakdown of three amino acids (leucine, isoleucine, and valine) that are present in protein-rich foods. Absence of this enzyme leads to accumulation of products that are toxic to cells and tissues, particularly in the nervous system.

    Treatment
    MSUD requires lifelong dietary control with strictly limited dietary protein and a specially formulated supplement. With careful dietary control, normal growth and development are possible.

    Contact
    MSUD Family Support Group
    Holmes Morton, M.D. Clinic for Special Children
    P.O. Box 128
    Strasburg, PA
    (717) 687-9407

  14. Mucolipidosis Type 4

    Estimated Carrier Frequency
    1 in 122

    Disease Incidence 1 in 62,500

    Symptoms
    Affected individuals have an intellectual disability, limited or absent speech, difficulty chewing and swallowing, weak muscles and problems controlling hand movements. Vision may be normal at birth but the clouding of the cornea and retinal degeneration lead to vision loss over the first decade of life.

    Causes
    The disease is caused by mutations in the MCOLN1 gene. MCOLN1 controls the production of a protein that plays a crucial role in cells’ ability to break down and reuse materials. The protein is particularly important to the functions of the brain, retina and stomach.

    Treatment
    There is no cure, but medication can reduce symptoms.

    Contact
    ML4 Foundation
    3500 Piedmont Road Suite 500
    Atlanta, Georgia 30305
    (877) 654-5459

  15. Nemaline Myopathy

    Estimated Carrier Frequency
    1 in 149

    Disease Incidence 1 in 112,896

    Symptoms
    Nemaline myopathy primarily affects skeletal muscles resulting in muscle weakness (myopathy) throughout the body, but it is typically most severe in the muscles of the face, neck, and limbs. This weakness can worsen over time. Respiratory failure can lead to early death.

    Causes
    A founder mutation in the NEB gene results in disorganization of the structure of the skeletal muscles. Inefficient muscle contraction causes muscle weakness and the other features of nemaline myopathy.

    Treatment
    At this time, there is no treatment or cure.

  16. Niemann-Pick Disease Type A

    Estimated Carrier Frequency
    1 in 90

    Disease Incidence 1 in 32,000

    Symptoms
    Children appear normal at birth, but this is followed by the progressive deterioration of the nervous system during infancy along with enlarged liver and spleen and failure to thrive. Lifespan is limited to early childhood.

    Causes
    Mutations in the SMPD1 gene lead to a deficiency of acid sphingomyelinase and the harmful accumulation of sphingomyelin, cholesterol, and other kinds of lipids within the cells and tissues of affected individuals.

    Treatment
    No cure is available for type A. Enzyme replacement research is ongoing.

    Contact
    National Niemann-Pick Disease Foundation P.O. Box 49
    401 Madison Avenue, Suite B
    Fort Atkinson, WI 53538
    (877) 287-3672
    (920) 563-0930

  17. Spinal Muscular Atrophy (SMA)

    Estimated Carrier Frequency
    1 in 41

    Symptoms
    Spinal Muscular Atrophy is a neuromuscular disease which causes a degeneration of the motor neurons in the spinal cord resulting in progressive muscular wasting. The age of onset varies from infancy to adulthood. The prognosis depends on age of onset. Affected individuals have normal IQ.

    Causes
    SMN1 gene mutations lead to a shortage of the SMN protein without which motor neurons die. Therefore, nerve impulses are not passed between the brain and muscles, which prevents muscles from performing their normal functions, leading to weakness.

    Treatment
    No cure exists, but there are treatments available to manage symptoms and prevent complications.

    Contact
    Spinal Muscular Atrophy Foundation
    888 Seventh Avenue, Suite 400
    New York, NY 10019
    NY Residents: (646) 253-7100
    (877) FUND-SMA

  18. Tay-Sachs Disease

    Estimated Carrier Frequency
    1 in 30

    Disease Incidence 1 in 3,000

    Symptoms
    Babies are born looking normal and gain milestones until 4 to 6 months, when they stop progressing and start to lose skills, have difficulty feeding and become less aware of their surroundings. Loss of vision and hearing, seizures and progressive neurologic deterioration occurs. The cherry red spot at the back of the eye is a characteristic finding. The lifespan limited to 4 to 6 years. A late onset form can affect adults and is not as severe.

    Causes
    The HEXA gene provides instructions for making part of an enzyme called beta-hexosaminidase A, which plays a critical role in the brain and spinal cord. Absence of this enzyme results in accumulation of GM2 ganglioside especially in the neurons of the brain and spinal cord leading to the destruction of these neurons and the symptoms of Tay-Sachs disease.

    Treatment
    No cure is available, but medication can prevent seizures. Gene therapy research is underway.

    Contact
    National Tay-Sachs and Allied Diseases Association
    2001 Beacon Street, Suite 204
    Boston, MA 02135
    (617) 277-4463

  19. Usher Syndrome Type 3

    Estimated Carrier Frequency
    1 in 107

    Disease Incidence 1 in 57,600

    Symptoms
    Usher syndrome comprises a group of diseases with a distinctive combination of hearing and progressive vision loss caused by retinitis pigmentosa, an inherited eye disease. Infants with Usher syndrome type III are usually born with normal hearing. Hearing loss typically begins during late childhood or adolescence, after the development of speech, and progresses over time. Vision problems also develop in late childhood or adolescence Some individuals will experience difficulties with balance due to inner ear problems. The IQ of affected individuals is normal.

    Causes
    A founder mutation in the CLRN1 gene leads 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 characteristic of this condition.

    Treatment
    Visual aids, hearing aids and cochlear implants can improve hearing and vision.

  20. Usher Syndrome Type 1F

    Estimated Carrier Frequency
    1 in 141

    Disease Incidence 1 in 86,436

    Symptoms
    Usher syndrome comprises a group of diseases with a distinctive combination of hearing and progressive vision loss caused by retinitis pigmentosa, an inherited eye disease. Infants with Usher syndrome type I are typically born completely deaf or lose most of their hearing within the first year of life. Progressive vision loss caused by retinitis pigmentosa occurs in childhood Problems with the inner ear affect balance. Children with type I sit and walk later than usual, but IQ is normal.

    Causes
    A founder mutation in the PCDH15 gene leads 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 characteristic of this condition.

    Treatment
    Unless children are fitted with a cochlear implant, they do not develop normal speech. Visual aids are available.

  21. Walker-Warburg Syndrome

    Estimated Carrier Frequency
    1 in 149

    Disease Incidence 1 in 90,000

    Symptoms
    Walker-Warburg syndrome affects the development of the muscles, brain and eyes, causing low muscle tone as well as eye and brain abnormalities. Survival is only into infancy or early childhood.

    Causes
    A founder mutation in the FKTN gene in the Ashkenazi population is associated with this condition. It prevents the production of any functional fukutin protein, which leads to the severe muscle, eye, and brain problems.

    Treatment
    Neither treatment nor cure is available at this time.

  22. More Information

    The Forward Staff has compiled a list of institutions that offer information about genetic diseases as well as support for patients and their families. Several organizations offer carrier screenings for people of Jewish heritage.

    American Autoimmune Related Diseases Association
    22100 Gratiot Ave.

    Eastpointe, MI 48021

    (586) 776-3900

    AARDA is the only national nonprofit health agency dedicated to bringing a national focus to autoimmunity, the major cause of serious chronic diseases. It is dedicated to the eradication of autoimmune diseases and the alleviation of suffering and the socioeconomic impact of autoimmunity through fostering and facilitating collaboration in the areas of education, public awareness, research, and patient services in an effective, ethical and efficient manner.

    Center For Jewish Genetics
    30 South Wells Street
    Chicago, IL 60606
    (312) 357-4718
    The Center for Jewish Genetics works to provide public and professional education and to empower community members to seek information and prevention strategies for Jewish genetic disorders and hereditary cancers.

    Genetic and Rare Diseases Information Center
    P.O. Box 8126
    Gaithersburg, MD 20898-8126
    (301) 251-4925
    The GARD Information Center provides timely access to experienced Information Specialists who provide current and accurate information about genetic and rare diseases in both English and Spanish.

    Genetic Disease Foundation
    1425 Madison Avenue, Box 1498
    New York, NY 10029
    (212) 659-6704
    The Genetic Disease Foundation provides support for research, education and efforts aimed at the prevention of genetic diseases.

    Global Genes Project
    28 Argonaut, Suite 150
    Aliso Viejo, CA 92656
    (949) 248-7273
    The Global Genes Project’s mission is to eliminate the challenges of rare disease by building awareness, and providing critical connections and resources to positively impact affected patients and families.

    Jewish Genetic Disease Consortium
    450 West End Avenue
    New York, NY 10024
    (855) 642-6900
    The Jewish Genetic Disease Consortium (JGDC) increases awareness about Jewish genetic diseases and encourages timely and appropriate carrier screening for all persons of Jewish heritage (at least one Jewish grandparent) as well as couples of interfaith marriage.

    National Organization For Rare Disorders
    55 Kenosia Avenue
    Danbury, CT 06810
    (203) 744- 0100
    The National Organization for Rare Disorders (NORD) is a federation of voluntary health organizations that are dedicated to helping people with rare “orphan” diseases through education, advocacy, research and other services.

    Program for Jewish Genetic Health of Yeshiva University/Einstein
    1300 Morris Park Avenue
    Bronx, NY 10461
    (718) 430-4156
    The Program for Jewish Genetic Health addresses Jewish genetic concerns from before birth to old age. It provides affordable and accessible testing for Tay-Sachs and other genetic diseases. In 2010, the program joined forces Yeshiva University to help better service the Jewish community.

    MyJewishGeneticsHealth.com
    MyJewishGeneticHealth.com is an online education resource conceived by the Program for Jewish Genetic Health of Yeshiva University/Albert Einstein College of Medicine that consists of individual “lessons” with topics selected based on their current relevance to the Jewish community, including specific diseases and medical conditions, genetic technologies and bioethical issues. It is designed to provide effective and accessible learning at the viewers’ convenience.

    Sephardic Health Organization for Referral and Education
    (646) 515-0473
    SHORE is a self-standing organization comprised of organizations, synagogues, prominent members, physicians, and spiritual leaders from the Sephardic community sharing a common goal of combating Sephardic Jewish genetic diseases. The mission is to increase awareness and educate the community about Sephardic Jewish genetic diseases, encourage genetic testing for carrier status and provide a source of information for affected individuals and their families.

    Victor Centers for the Prevention of Jewish Genetic Diseases
    Einstein Medical Center Philadelphia, 5501 Old York Road, Levy 2 West
    Philadelphia, PA 19141
    (877) 401-1093
    The Victor Centers for Jewish Genetic Diseases provide education, genetic counseling and carrier screening for Jewish genetic diseases. Victor Centers are located in Philadelphia, Boston and Miami.

Author

Forward Staff

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