$Unique_ID{BRK04341} $Pretitle{} $Title{X-Linked Lymphoproliferative Syndrome} $Subject{X-Linked Lymphoproliferative Syndrome Immunodeficiency X-Linked Progressive Combined Variable Duncan Disease X-Linked Lymphoproliferative Disease XLPD XLP EBV Susceptibility EBVS Immunodeficiency-5 IMD5 Infectious Mononucleosis Susceptibility IMS Chronic Fatigue Syndrome Infectious Mononucleosis Malignant Lymphoma Non-Hodgkin's Hypogammaglobulinemia } $Volume{} $Log{} Copyright (C) 1989 National Organization for Rare Disorders, Inc. 729: X-Linked Lymphoproliferative Syndrome ** IMPORTANT ** It is possible that the main title of the article (X-Linked Lymphoproliferative Syndrome) is not the name you expected. Please check the SYNONYM listing to find the alternate names and disorder subdivisions covered by this article. Synonyms Immunodeficiency, X-Linked Progressive Combined Variable Duncan Disease X-Linked Lymphoproliferative Disease XLPD XLP EBV Susceptibility EBVS Immunodeficiency-5 IMD5 Infectious Mononucleosis Susceptibility IMS Information on the following diseases can be found in the Related Disorders section of this report: Chronic Fatigue Syndrome Infectious Mononucleosis Malignant Lymphoma, Non-Hodgkin's Hypogammaglobulinemia General Discussion ** 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. X-linked Lymphoproliferative Syndrome is a very rare life-threatening genetic disease of the immune system that affects only males, making them vulnerable to death from the Epstein-Barr Virus which causes mononucleosis. Symptoms X-Linked Lymphoproliferative Syndrome (XLP) is a rare inherited immune deficiency. Most people are exposed to the Epstein Barr virus during childhood or adolescence, and they recover from infectious mononucleosis without long lasting effects. However, mononucleosis in males with the XLP defect can be life-threatening. Additionally, these males are susceptible to other life-threatening diseases such as lymphomas and hypogammaglobulinemia. There are usually no symptoms of XLP until the patient contracts the Epstein-Barr virus. When this happens the person becomes extremely ill with infectious mononucleosis, or non-Hodgkin's malignant lymphoma, or hypogammaglobulinemia (an insufficient level of gammaglobulin in the body which is needed to fight off common infections). The disease can be fatal in 60 to 75% of these male patients. Causes The cause of X-Linked Lymphoproliferative Syndrome is thought to be a rare recessive genetic defect located on the X chromosome. 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. Scientists are still working to find the exact location of the defective gene that causes X-Linked Lymphoproliferative Syndrome. Affected Population X-Linked Lymphoproliferative Syndrome affects only males who carry the defective gene and who become infected by the Epstein-Barr virus. The great majority of adults in the U.S. have been exposed to the E-B virus by the time they reach adulthood. In many cases mononucleosis is very mild during childhood and is misdiagnosed as a sore throat or nonspecific viral infection. Immunity lasts throughout life once a person has been infected. Related Disorders The following disorders may have symptoms that are similar to mononucleosis. However, people with XLP have more intense life threatening symptoms: Chronic Fatigue Syndrome is characterized by severe fatigue that lasts for weeks or months and is severe enough to significantly limit daily activities. Symptoms include mild fever, sore throat, painful lymph nodes in the neck or armpits, generalized weakness of muscles with pain or discomfort, headaches, joint pains that come and go, vision problems, or sleep disturbances. Symptoms often begin following a flu-like illness. The intense fatigue can mimic weakness associated with mononucleosis, but the Epstein Barr virus is not related to Chronic Fatigue Syndrome. (For more information on this disorder, choose "Chronic Fatigue" as your search term in the Rare Disease Database). Infectious Mononucleosis is a common infectious disease caused by the Epstein-Barr virus that is also known as the "kissing disease" or "Glandular Fever." Symptoms include fever, severe fatigue, swollen lymph glands, and an abnormally large number of white blood cells in the blood. These white blood cells can look like certain leukemia cells that sometimes tests are needed to determine exactly which disease the patient has. In mild cases the disorder may not be diagnosed because it appears like a mild viral infection. In more severe cases it may take 6 to 8 weeks or longer for recovery which usually occurs without treatment. Malignant Lymphoma is a type of cancer that appears most often in the lymph nodes, spleen, or other normal sites of lymphoreticular cells. It may invade the blood and manifest itself as leukemia. It can be located in almost any part of the body. There are many different types of Lymphoma that are classified by cell type, degrees of differentiation, and nodular pattern. Hypogammaglobulinemia is a disorder of antibody production and/or function which cannot be attributed to some other underlying illness. Low levels of gammaglobulin leads to insufficient antibodies that are needed to resist and overcome common infections. People with this disorder are susceptible to infections that can become life-threatening due to their impaired immune system. (For more information on this disorder, choose "Agammaglobulinemia" as your search term in the Rare Disease Database). Therapies: Standard Treatment of X-Linked Lymphoproliferative Syndrome is symptomatic and supportive. In cases of hypogammaglobulinemia, gammaglobulin can be prescribed to boost the immune system. Genetic counseling will be of benefit for patients and their families. Therapies: Investigational Scientists are studying the chromosomes of X-Linked Lymphoproliferative Syndrome patients through DNA probes. It is hoped that the gene defect which causes this syndrome will be identified in the near future. The drug recombinant interferon-gamma (IFN-gamma) is being tested as a possible treatment for XLP. More studies are necessary to determine safety and effectiveness of this treatment. This disease entry is based upon medical information available through January 1990. 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 X-linked Lymphoproliferative Syndrome, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 NIH/National Institute of Allergy and Infectious Diseases 9000 Rockville Pike Bethesda, MD 20892 (301) 496-5717 Physicians may refer patients with XLP who wish to participate in genetic studies to: Dr. James Skare Boston University School of Medicine Center for Human Genetics Boston, MA 02118 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, 8th ed.: Victor A. McKusick; Johns Hopkins University Press, 1986. Pp. 1329. MARKERS MAPPED FOR LIFE-THREATENING DISORDER, James Skare, Research Resources Reporter, National Institutes of Health (June, 1989, issue XIII (6)). Pp. 6-7. MALIGNANT LYMPHOMA IN THE X-LINKED LYMPHOPROLIFERATIVE SYNDROME. D.S. Harrington, et al.; Cancer, (April 15, 1987, issue 59 (8)). Pp. 1419-1429. EPSTEIN-BARR VIRUS INFECTIONS IN MALES WITH THE X-LINKED LYMPHOPROLIFERATIVE SYNDROME, H. Grierson, et al.; Ann Intern Med, (April, 1987, issue 106 (4)). Pp. 538-545. X-LINKED LYMPHOPROLIFERATIVE DISEASE: A KARYOTYPE ANALYSIS, A. Harris, et al.; Cytogenet Cell Genet, (1988, issue 47 (1-2)). Pp. 92-94. INTERFERON-GAMMA IN A FAMILY WITH X-LINKED LYMPHOPROLIFERATIVE SYNDROME WITH ACUTE EPSTEIN-BARR VIRUS INFECTION. M. Okano, et al.; J Clin Immunol (January, 1989, issue 9 (1)). Pp. 48-54.