$Unique_ID{BRK04335} $Pretitle{} $Title{Wiskott-Aldrich Syndrome} $Subject{Wiskott-Aldrich Syndrome WAS Immunodeficiency with Thrombocytopenia and Eczema Aldrich syndrome Eczema-Thrombocytopenia-Infection Syndrome Immunodeficiency, Wiskott-Aldrich Type Immunodeficiency-2 IMD-2} $Volume{} $Log{} Copyright (C) 1986, 1987, 1988, 1993 National Organization for Rare Disorders, Inc. 76: Wiskott-Aldrich Syndrome ** IMPORTANT ** It is possible that the main title of the article (Wiskott-Aldrich Syndrome) is not the name you expected. Please check the SYNONYMS listing to find the alternate name and disorder subdivisions covered by this article. Synonyms WAS Immunodeficiency with Thrombocytopenia and Eczema Aldrich syndrome Eczema-Thrombocytopenia-Infection Syndrome Immunodeficiency, Wiskott-Aldrich Type Immunodeficiency-2 IMD-2 Information on the following diseases can be found in the Related Disorders section of this report: Primary Agammaglobulinemias (X-Linked Immunodeficiency Syndrome) Severe Combined Immunodeficiency DiGeorge Syndrome Nezelof Syndrome Ataxia Telangiectasia ** REMINDER ** The Information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. Wiskott-Aldrich Syndrome is a rare inherited disorder (X-linked) characterized by an immune deficiency primarily affecting B lymphocytes, scaly red skin rashes (eczema), and abnormally low levels of circulating blood platelets (thrombocytopenia). The B lymphocytes are specialized white blood cells of the immune system that search out and attack bacteria, viruses, or other foreign substances in the body. The symptoms of Wiskott- Aldrich Syndrome may vary greatly among patients. Children with this disorder can face life-threatening complications of thrombocytopenia and immunodeficiency prior to adulthood. Symptoms The symptoms of Wiskott-Aldrich Syndrome generally begin during infancy. Excessive bleeding (hemorrhage) from circumcision or minor trauma is common in infants with this disorder. Bleeding may occur from the intestines and hemorrhaging may be severe. The skin may have small red spots (petechiae) and/or purplish discolorations due to the leakage of blood under the skin (thrombocytopenic purpura). In addition, infants with Wiskott-Aldrich Syndrome may have chronic red, scaly rashes on the skin (eczema). Male children with Wiskott-Aldrich Syndrome have defects in their resistance to infections. These defects occur because of the inability of T lymphocytes to properly resist infectious disease (cell-mediated immunity). T lymphocytes, also known as "killer cells," assist B lymphocytes to respond to infection and other foreign agents that invade the body. Defects also occur in the development and the continuing presence of circulating antibodies in the blood (humoral immunity). The most outstanding immune defect in infants with Wiskott-Aldrich Syndrome is the inability to produce antibodies to certain complex carbohydrates (polysaccharide antigens). Children with this disorder are highly susceptible to infections with particular organisms that have coverings or are "encapsulated," since these coverings contain polysaccharides. These encapsulated organisms include pneumococcus and Hemophilus influenzae. Children with Wiskott-Aldrich Syndrome commonly experience infections of the middle ear (otitis media), acute inflammation of the lungs (pneumonia), inflammation of the membranes that cover the brain and spinal cord (meningitis), and systemic infection with bacteria present in the blood stream (sepsis). Cell-mediated immunity and T cell function become progressively worse as a child with Wiskott-Aldrich Syndrome ages. Fungal and viral infections can become serious problems late in the course of the disorder. Pneumocystis carinii (a bacteria that causes pneumonia) and herpes virus infections are also common. Other symptoms of Wiskott-Aldrich Syndrome include an abnormally enlarged spleen (splenomegaly) and anemia. People with this disorder have a 10 percent chance of developing malignancies, particularly leukemia and lymphoma. (For more information on these disorders, choose "Anemia," "Leukemia," and "Lymphoma" as your search term in the Rare Disease Database.) People with Wiskott-Aldrich Syndrome have normal levels of total antibodies in their blood; however, the proportions of different antibodies are abnormal. Cells that later produce platelets (precursors) appear normal under a microscope, but platelets circulating in the blood stream have both structural and functional abnormalities. Causes Wiskott-Aldrich Syndrome is inherited as an autosomal recessive X-linked genetic trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother. X-linked recessive disorders are conditions which are coded on the X chromosome. Females have two X chromosomes, but males have one X chromosome and one Y chromosome. Therefore, in females, disease traits on the X chromosome can be masked by the normal gene on the other X chromosome. Since males only have one X chromosome, if they inherit a gene for a disease present on the X, it will be expressed. Men with X-linked disorders transmit the gene to all their daughters, who are carriers, but never to their sons. Women who are carriers of an X-linked disorder have a fifty percent risk of transmitting the carrier condition to their daughters, and a fifty percent risk of transmitting the disease to their sons. The defective gene that causes Wiskott-Aldrich Syndrome is located on the short arm of the X chromosome (p11.4-p11.21). Males get the more severe form of the disorder. Affected Population Wiskott-Aldrich Syndrome is a rare disorder that affects more males than females. Females can get a milder form of the disorder, or be a carrier with no symptoms. Related Disorders Symptoms of the following disorders can be similar to those of Wiskott- Aldrich Syndrome. Comparisons may be useful for a differential diagnosis: Primary Agammaglobulinemias (X-linked Immunodeficiency) are a group of inherited immune deficiencies characterized by insufficient antibodies. The most frequent symptoms of these disorders are usually repeated bacterial infections. Bacteria infections are a frequent cause of chronic inflammation of the intestines and diarrhea. Repeated infections of the middle ear and respiratory tract may also occur. Areas of patchy, reddish skin may appear around the eyes, fingers, knees, and ankles. Some children with Primary Agammaglobulinemias experience joint swelling and pain. (For more information on this disorder, choose "Primary Agammaglobulinemias" as your search term in the Rare Disease Database.) Severe Combined Immunodeficiency (SCID) is a group of rare, congenital disorders characterized by little or no immune response. A person with this disorder is susceptible to recurring infections with bacteria, viruses, fungi, and other infectious agents. If untreated, this disorder may result in frequent, severe infections, growth retardation, and can be life- threatening. Other symptoms of this disorder may include weight loss, weakness, infections of the middle ear, and skin infections. (For more information on this disorder, choose "Severe Combined Immunodeficiency" as your search term in the Rare Disease Database.) DiGeorge Syndrome is a very rare immune deficiency that results from developmental defects in the thymus and parathyroid glands. This disorder is characterized by seizures during the first few days of life due to the abnormal function of the parathyroid gland. Inability to fight off frequent infections from viruses, fungi, and other bacteria is characteristic of this disorder. Children with DiGeorge Syndrome frequently have chronic nasal infections, diarrhea, oral candidiasis, and Pneumocystis pneumonia. (For more information on this disorder, choose "DiGeorge" as your search term in the Rare Disease Database.) Nezelof Syndrome is a rare immune deficiency disorder characterized by the impairment of cellular immunity against infections. Symptoms of this disorder may include frequent and severe infections from birth including oral candidiasis, diarrhea, skin infections, septicemia, urinary tract infections, measles, pulmonary infections, and vaccinia. Typically a child with this disorder may be mentally retarded and have a progressive loss of muscle tissue. (For more information on this disorder, choose "Nezelof" as your search term in the Rare Disease Database.) Ataxia Telangiectasia is a severe, rare, inherited neurological disorder characterized by the progressive loss of motor coordination in the arms, legs, and head (cerebellar ataxia). Some cases of this disorder are associated with immunodeficiencies (IgA or IgE). Mental development may be normal in the early stages of the disease, but progressive dementia may occur. This disease usually begins in infancy but may not be apparent until the child is school age. Classic red spots or telangiectasia appear in the eyes, and later on the face and roof of the mouth. (For more information on this disorder, choose "Ataxia Telangiectasia" as your search term in the Rare Disease Database.) Therapies: Standard Children with Wiskott-Aldrich Syndrome are treated regularly with transfer factor, a substance derived from lymphocytes. About 50 percent of patients experience a restoration of the proper function of blood cells and the immune system. This factor also improves the itchy red rashes (eczema) associated with this disorder. Researchers are studying bone marrow transplantation from a compatible donor (allogenic) as a possible treatment for some cases of Wiskott-Aldrich Syndrome. Patients treated with this procedure receive high doses of chemotherapy, followed by radiation therapy. Then donor bone marrow cells are given intravenously to the patient. It is hoped that this procedure may lead to the improvement of the blood abnormalities and immune deficiencies associated with Wiskott-Aldrich Syndrome. A complication of this procedure may be Graft versus Host Disease, has also been used with some success in a few patients. (For more information on this disorder, choose "Graft versus Host" as your search in the Rare Disease Database.) Children with Wiskott-Aldrich Syndrome who do not respond well to transfer factor, are given antibodies intravenously and antibiotics that may help reduce susceptibility to infectious disease. Excessive abnormal bleeding, a complication of thrombocytopenia, may be managed by administering carefully purified platelet concentrates or the surgical removal of the spleen (splenectomy). While effective in reducing the risk of bleeding, splenectomy further increases the risk of serious infection with a variety of organisms. Most of the patients will require continued intravenous antibiotic and/or gammaglobulin treatment to prevent infections. Platelet transfusions are not without problems, since repeated transfusions are likely to stimulate the formation of platelet antibodies. The standard drugs for thrombocytopenia, corticosteroids and immunosuppressants, have no role in the treatment of Wiskott-Aldrich Syndrome since these drugs cause a further decrease in immune function. Vincristine may be a useful drug in the treatment of cancer associated with this disorder, since it has anti-tumor activity and helps improve platelet function. Vincristine does not suppress the immune system. Infectious disease in children with Wiskott-Aldrich Syndrome requires vigorous therapy with antifungal, antibiotic, and supportive measures. Pneumonia caused by Pneumocystis carinii can be particularly difficult to treat; the 2 drugs usually used are trimethoprim-sulfamethoxazole and pentamidine isethionate. (For more information on treatment of P. carinii pneumonia, choose "AIDS" as your search term in the Rare Disease Database.) Cytomegalovirus and generalized herpes simplex infections may be treated with acyclovir, ganciclovir (DHPG), idoxuridine, floxuridine, or cytarabine. Severe Candida and related fungal infections usually respond well to amphotericin B therapy. (For more information on this disorder, choose "Cytomegalovirus" as your search term in the Rare Disease Database.) Prevention of infection is extremely important. Every attempt should be made to protect people with Wiskott-Aldrich Syndrome from infectious disease. Immunization with live virus vaccines should probably be avoided. Genetic counseling will be of benefit for patients and their families. Other treatment is symptomatic and supportive. Therapies: Investigational Scientists are studying the role and functions of genes through the National Institutes of Health's Human Genome Project. It is hoped that they may identify the protein that is defective in Wiskott-Aldrich Syndrome so that a treatment may be developed to correct the genetic abnormality that causes this disorder. This disease entry is based upon medical information available through June 1993. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on Wiskott-Aldrich Syndrome, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 Immune Deficiency Foundation 3565 Ellicott Mill Drive, Unit B2 Ellicott City, MD 21043 (800) 296-4433 (410) 461-3127 NIH/National Institute of Allergy and Infectious Diseases (NIAID) 9000 Rockville Pike Bethesda, MD 20892 (301) 496-5717 NIH/National Cancer Institute (NCI) 9000 Rockville Pike, Bldg. 31, Rm. 1A2A Bethesda, MD 20892 (800) 4-CANCER The National Cancer Institute has developed PDQ (Physician Data Query), a computerized database designed to give doctors quick and easy access to many types of information vital to treating patients with this and many other types of cancer. To access this service, a doctor can contact the Cancer Information Service offices at 1-800-4-CANCER. Information specialists at this toll-free number can answer questions about cancer prevention, diagnosis, and treatment. For Genetic Information and Genetic Counseling Referrals: March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue White Plains, NY 10605 (914) 428-7100 Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 (800) 336-GENE (301) 652-5553 References MENDELIAN INHERITANCE IN MAN, 10th Ed.: Victor A. McKusick, Editor: Johns Hopkins University Press, 1992. Pp. 1781-83. CECIL TEXTBOOK OF MEDICINE, 19th Ed.: James B. Wyngaarden, and Lloyd H. Smith, Jr., Editors; W.B. Saunders Co., 1990. Pp. 1451-52, 1578. THE MERCK MANUAL, 16th Ed.: Robert Berkow Ed.; Merck Research Laboratories, 1992. Pp. 305, 315. HEMATOLOGY, 4th Ed,: William J. Williams, et al,; Editors; McGraw-Hill, Inc., 1990. Pp. 964-969. BIRTH DEFECTS ENCYCLOPEDIA, Mary Louise Buyse, M.D., Editor-In-Chief; Blackwell Scientific Publications, 1990. Pp. 963-64. NELSON TEXTBOOK OF PEDIATRICS, 14th Ed.; Richard E. Behrman et al; W.B. Saunders Co., 1992. Pp. 555, 1280. IMMUNODEFICIENCY. Buckley, R.H. J Allergy Clin Immunol Dec 1983; 72(6):627-641. WISKOTT-ALDRICH SYNDROME: NEW MOLECULAR AND BIOCHEMICAL INSIGHTS. M. Peacocke; J Am Acad Dermatol (Oct 1992; 27(4)). Pp. 507-19. EVIDENCE FOR DEFECTIVE TRANSMEMBRANE SIGNALING IN B CELLS FROM PATIENTS WITH WISKOTT-ALDRICH SYNDROME. H.U. Simon; J Clin Invest (Oct 1992; 90(4)). Pp. 1396-405. EARLY BONE MARROW TRANSPLANTATION IN AN INFANT WITH WISKOTT-ALDRICH SYNDROME. L.J. Beard; Am J Pediatr Hematol Oncol (Fall 1992; 13(3)). Pp. 310-14. BONE MARROW TRANSPLANTATION FOR GENETIC DISORDERS. J.A. Brochstein; Oncology (March 1992; 6(3)). Pp. 51-58, 63-66.