All About Genetic Diseases That Strike Sephardic Jews

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The Forward Staff has compiled a guide to the most common heritable “Sephardic Jewish diseases,” with information on symptoms, causes and carrier rates for each, as well as the geographic regions from which affected Jewish populations originate.

These diseases are mostly caused by recessive genetic mutations, 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 with at least one partner of Sephardic or Mizrahi origin are encouraged to undergo screening if they plan to have children.

Unlike Ashkenazi Jews, who share ethnic commonalities regardless of country of origin,” Sephardi” is a broad label. Subgroups like Moroccan Jews or Iranian Jews have distinct characteristics, making universal screening panels for inherited genetic diseases for all Sephardic and Mizrahi Jews impractical. Therefore, it’s best to discuss one’s family heritage with a doctor or genetic counselor in order to receive screening recommendations.

The Sephardic Health Organization for Referral and Education recommends that non-Ashkenazi Jewish couples get tested for the 19 most common Ashkenazi Jewish diseases as well — because some of the diseases, such as cystic fibrosis and spinal muscular atrophy, can also be found among non-Ashkenazi populations. Screenings usually require blood samples.

Data on the estimated carrier frequency and the affected Jewish population are courtesy of the Jewish Genetic Disease Consortium in New York.

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. Alpha Thalassemia

    Affected Jewish Populations
    Iraq, Yemen, Morocco, Kurdistan

    Estimated Carrier Frequency
    1 in 4 to 1 in 100

    Symptoms
    Alpha thalassemia is a blood disorder that reduces the production of hemoglobin, the protein in red blood cells that carries oxygen to cells throughout the body. There are 2 clinically significant forms: Hb Bart syndrome is usually fatal in infancy. Hemoglobin H disease causes mild to moderate anemia, enlarged spleen and liver, and jaundice.

    Causes
    Alpha thalassemia typically results from deletions involving the HBA1 and HBA2 genes, both of which are needed to make a protein called alpha-globin, which is a subunit of hemoglobin. If there is loss of function of one or more of these genes, there is decreased alpha globin formed. This results in abnormal hemoglobin that cannot carry oxygen effectively to all parts of the body.

    Treatment
    There is no effective treatment for Hb Bart syndrome. Anemia caused by HbH disease can be managed with blood transfusions.

    Contact
    Thalassemia Support Foundation

    Cooley’s Anemia Foundation 330 Seventh Avenue, #200
    New York, NY 10001
    (800)522-7222

  2. Ataxia Telangiectasia

    Affected Jewish Populations
    North Africa

    Estimated Carrier Frequency
    1 in 80

    Symptoms
    First symptoms appear before the age of 5 and include difficulty controlling body movements (ataxia) such as those needed for walking and speech. Spiderlike veins appear at the corners of the eyes and on ears and cheeks (telangiectasia). Individuals have a weakened immune system and are at increased risk for cancers. Patients typically live into early adulthood.

    Causes
    The ATM gene codes for a protein that is involved in cell division and DNA repair. Mutations in the gene prevent normal functioning, causing DNA breaks that can lead to tumors. The cerebellum, the part of the brain that controls movement, is particularly affected by the loss of the protein.

    Treatment
    Immunoglobulin G replacement therapy can help guard against infections.

  3. Beta Thalassemia

    Affected Jewish Populations
    Mizrahi, Sephardic

    Estimated Carrier Frequency
    1 in 5 to 1 in 7

    Symptoms
    Beta thalassemia is a blood disorder that reduces the production of hemoglobin and can be classified into two types: Thalassemia intermedia causes anemia, bone deformities and an enlarged spleen. It requires blood transfusions. The more severe form is called thalassemia major or Cooley’s anemia, which is a severe disease that requires regular transfusions to survive.

    Causes
    The HBB gene codes for a protein that makes beta-globin, which is a subunit of hemoglobin. Hemoglobin carries the oxygen to the cells of the body. Without sufficient hemoglobin, red blood cells do not develop normally and anemia results. Some mutations in HBB prevent the production of any beta-globin and cause thalassemia major. Other mutations result in reduced amounts of beta-globin and may cause thalassemia intermedia, a milder but still severe disorder.

    Treatment
    People affected by thalassemia major require life-long blood transfusions as well as chelation therapy to prevent organ failure from iron overload.

    Contact
    Thalassemia Support Foundation

    Cooley’s Anemia Foundation 330 Seventh Avenue, #200
    New York, NY 10001
    (800)522-7222

  4. Corticosterone Methyloxidase Type 2 Deficiency

    Affected Jewish Populations
    Iran

    Estimated Carrier Frequency
    1 in 30

    Symptoms
    This salt-losing disorder, also known as congenital hypoaldosteronism, manifests itself in the first weeks of life, as too much salt and too little potassium are released in the urine. Infants have poor growth, weakness and dizziness. In severe cases, and if left untreated, it can lead to vomiting, coma and death. Early detection and treatment lead to normal development and life span, and symptoms can disappear by adulthood.

    Causes
    Mutations in the gene CYP11B2 cause a defect in the synthesis of aldosterone, which helps maintain proper salt and fluid levels in the body.

    Treatment
    Early detection and ongoing treatment can lead to milder or no symptoms by adulthood.

  5. Costeff Optical Atrophy

    Affected Jewish Populations
    Iran, Iraq

    Estimated Carrier Frequency
    1 in 10

    Symptoms
    In the first few years of life, patients experience a progressive loss of clear vision along with involuntary jerky physical movements. Some affected individuals lose their ability to walk. Mild cognitive deficits can also occur.

    Causes
    Mutations in the OPA3 gene, which codes for a protein that is also found in mitochondria, the cells’ “power plant,” have been associated with the disease. The exact function of the protein is not understood.

    Treatment
    There is no cure.

  6. Cystic Fibrosis

    Affected Jewish Populations
    all Sephardic and Mizrahi

    Estimated Carrier Frequency
    1 in 26

    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)

  7. Familial Mediterranean Fever

    Affected Jewish Populations
    Iran, Iraq, Mediterranean

    Estimated Carrier Frequency
    1 in 3 to 1 in 7

    Symptoms
    Patients experience recurrent episodes of painful inflammation in the abdomen, chest of joints, which are often accompanied by fever. The episodes last usually from 12 to 72 hours. They return with variable frequency; sometimes year may pass between episodes. If left untreated, amyloidosis, a potentially dangerous buildup of protein in organs and tissues, can occur.

    Causes
    Mutations of the MEFV gene reduce the effects of the body’s natural pyrin proteins, which is involved in the immune system as it regulates the process of inflammation. Reduced pyrin protein results in a prolonged response to inflammation, resulting in the symptoms of familial Mediterranean fever.

    Treatment
    Lifelong treatment with colchicine, an anti-inflammation medication that is also used for gout, prevents the attacks and the deposition of amyloid.

  8. Glycogen Storage Disease Type 3

    Affected Jewish Populations
    North Africa

    Estimated Carrier Frequency
    1 in 35

    Symptoms
    Also known as Cori disease, the first indicator in children is usually a swollen belly caused by enlargement of the liver. Infants also have low blood sugar. The disease is accompanied by poor muscle tone.

    Causes
    Mutations in the AGL gene cause an enzyme deficiency that impairs the breakdown of glycogen, a carbohydrate that powers the body during times of fasting and exercise. The progressive buildup of glycogen impairs the function of certain organs and tissues, especially the liver and skeletal muscles.

    Treatment
    A diet high in proteins and frequent feeds keeps the blood sugar of infants stable. After age 1, daily doses of cornstarch and high protein intake can maintain health.

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

  9. G6PD Deficiency

    Affected Jewish Populations
    Kurdistan

    Estimated Carrier Frequency
    1 in 2 (Kurdish), 1 in 4 (Iraqi)

    Symptoms
    Most people with this form of anemia don’t have any symptoms unless exposed to certain triggers, such as drugs (aspirins), foods (mostly legumes) and infections. These stressors cause red blood cells to rupture, resulting in hemolytic anemia. Most people recover once the trigger is removed, and rarely develop chronic anemia.

    Causes
    The disease is caused by deficient glucose-6-phosphate dehydrogenase (G6PD), an enzyme that helps protect red blood cells from damage and premature destruction. Because the underlying mutation on the G6PD gene is located on the X sex chromosome, most cases occur in men. Women who carry one mutation are generally not affected because the normal copy of the gene on their second X chromosome compensates for the defect.

    Treatment
    Affected individuals are healthy if they avoid triggers, and receive medical care for episodes of anemia.

  10. Hereditary Inclusion Body Myopathy

    Affected Jewish Populations
    1 in 10 to 1 in 20

    Estimated Carrier Frequency
    Iran

    Symptoms
    First symptoms of this neuromuscular disorder usually occur in the 20s, and include loss of balance and weakness of the fingers and legs. The progressive loss of muscle tissue confines many patients to wheelchairs, but does not affect the brain, internal and sensory organs.

    Causes
    It is caused by mutations in the GNE gene, which codes for an enzyme that is required for the production of sialic acid, a sugar necessary for cellular functions. Mutations in the GNE gene lead to decreased production of sialic acid, causing weakness in skeletal muscles.

    Treatment
    There is currently no cure.

  11. Limb-Girdle Muscular Dystrophy Type 2B

    Affected Jewish Populations
    1 in 10 to 1 in 25

    Estimated Carrier Frequency
    Libya, Yemen, Caucasus

    Symptoms
    Affected individuals usually experience the first symptoms, which include weak thigh muscles and fatigue, in their mid-20s. The muscle wasting progresses to the upper body, resulting in difficulties with lifting arms over the head. About 21 years after the onset, individuals are typically wheelchair-bound. Respiratory and heart muscles are usually not affected.

    Causes
    This subtype, also known as dysferlinopathy, is caused by mutations in the DYSF gene, which prevent the normal production of a protein (dysferlin) involved in muscle maintenance and repair.

    Treatment
    There is no cure, but physical therapy and stretching can help maintain muscle strength and flexibility.

    Contact
    Muscular Dystrophy Association — USA
    222 S. Riverside Plaza, Suite 1500
    Chicago, IL 60606
    (800) 572-1717

  12. Metachromatic Leukodystrophy

    Affected Jewish Populations
    1 in 4

    Estimated Carrier Frequency
    Yemen Habbani

    Symptoms
    The most common form of this disease, which is characterized by the progressive loss of neurological and movement abilities, is the late infantile form: In their second year, children progressively lose their ability to speak, walk, hear and see, and eventually develop spasms and become unresponsive. They usually do not survive childhood. The juvenile form has its onset between ages 4 and 14, and the early symptoms include clumsiness, behavior problems and incontinence. The later stages are the same as the infantile form, though progression is slower. The adult form shows its first symptoms after sexual maturity, and includes personality changes, loss of control over emotions and seizures. The decline can last 20-30 years, with the final stages similar to early-onset forms. The type is usually similar within a family.

    Causes
    Mutations in the gene ARSA cause impaired functioning of an enzyme involved in the breakdown of chemicals called sulfatides. As they build up to toxic levels, they damage the protective myelin sheath that surrounds nerve cells and destroy the nervous system.

    Treatment
    There is no cure, but supportive treatment can help preserve quality of life.

    ContactUnited Leukodystrophy Foundation
    224 N. Second Street, Suite 2
    Dekalb, IL 60115
    (800) 728-5483
    local call: (815) 748- 3211

  13. Normophosphatemic Familial Tumoral Calcinosis

    Affected Jewish Populations
    1 in 92

    Estimated Carrier Frequency
    Yemen

    Symptoms
    In the first year of life, affected infants show reddish-to-hyperpigmented skin lesions. These develop into solid, raised bumps that contain calcium and often open and leak. The lesions are life-threatening. Inflammation of the eyes and gums is also common.

    Causes
    The SAMD9 gene codes for a protein that is thought to be involved in the skin’s reaction to inflammation and cell growth. Mutations prevent normal functioning.

    Treatment
    No effective treatment or cure exists yet.

  14. Polyglandular Deficiency Syndrome

    Affected Jewish Populations
    1 in 40

    Estimated Carrier Frequency
    Iran

    Symptoms
    The symptoms of this autoimmune disorder, which is usually diagnosed in childhood or adolescence, depend on which glands are affected: Hypoparathyroidism, the decreased function of the parathyroid glands, causes muscle cramping and tingling sensations in lips, fingers and toes. Adrenal insufficiency can cause Addison’s disease, the symptoms of which include muscle weakness, fatigue and low blood sugar. Oral candidiasis, a fungal infection of the mouth, is also common.

    Causes
    Mutations in the AIRE gene impair the function of the autoimmune regulator protein, damaging the glands and causing the immune system to attack its own body.

    Treatment
    Hormone replacement therapy is available.

  15. Pseudocholinesterase Deficiency

    Affected Jewish Populations
    1 in 10

    Estimated Carrier Frequency
    Iran, Iraq

    Symptoms
    Also known as anesthesia sensitivity, affected individuals overreact to muscle relaxants, which are given during surgery. Skeletal muscles, including those that are involved in breathing, remain paralyzed after surgery.

    Causes
    The BCHE gene provides instructions for producing the enzyme pseudocholinesterase, which is involved in the breakdown of muscle relaxants known as coline ester drugs. Mutations impair the functions of the enzyme, causing prolonged effects of the drugs (up to several hours).

    Treatment
    Patients are given mechanical ventilatory support until the paralysis of the respiratory muscles resolves.

  16. Spinal Muscular Atrophy Type 1A

    Affected Jewish Populations
    1 in 10

    Estimated Carrier Frequency
    Egypt

    Symptoms
    Also known as Werdnig-Hoffman disease, affected infants display severe muscle weakness at birth or in the first months of life. Most are unable to lift their head or sit unassisted; some have difficulty breathing or swallowing. Most children die by the age of 2.

    Causes
    Mutations in the SMN1 gene cause a shortage of the SMN protein, which is involved in the maintenance of motor neurons. Without this protein, motor neurons die and nerve impulses cannot be passed between brain and muscles.

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

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

  17. Wolman's Disease

    Affected Jewish Populations
    1 in 45

    Estimated Carrier Frequency
    Iran, Bukhara

    Symptoms
    The symptoms of this fat storage disorder usually appear in the first months of life, and include vomiting, diarrhea and difficulty gaining weight. Enlarged liver and spleen with harmful amounts of lipids are other symptoms. Most affected children develop severe malnutrition because the body cannot use lipids properly and die in infancy.

    Causes
    The LIPA gene codes for the enzyme lysosomal acid lipase, which plays an instrumental role in processing lipids. When the gene is defective, the body cannot metabolize certain types of fats. Consequently, fats build up in body tissue and become toxic to the organs.

    Treatment
    There is no approved treatment, but experimental therapies, such as stem cell transplants are being tried. Symptomatic treatment is offered.

  18. 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.

    MyJewishGeneticHealth.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.

Written by

Forward Staff

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