X-linked lymphoproliferative disease
X-linked lymphoproliferative disease ( XLP ) is a disorder of the immune system and blood-forming cells that is found almost exclusively in males. More than half of individuals with this disorder experience an exaggerated immune response to the Epstein-Barr virus (EBV). EBV is a very common virus that eventually infects most humans. In some people it causes infectious mononucleosis (commonly known as "mono"). Normally, after initial infection, EBV remains in certain immune system cells (lymphocytes) called B cells. However, the virus is generally inactive (latent) because it is controlled by other lymphocytes called T cells that specifically target EBV-infected B cells.
People with XLP may respond to EBV infection by producing abnormally large numbers of T cells, B cells, and other lymphocytes called macrophages. This proliferation of immune cells often causes a life-threatening reaction called hemophagocytic lymphohistiocytosis. Hemophagocytic lymphohistiocytosis causes fever, destroys blood-producing cells in the bone marrow, and damages the liver. The spleen, heart, kidneys, and other organs and tissues may also be affected. In some individuals with XLP. hemophagocytic lymphohistiocytosis or related symptoms may occur without EBV infection.
About one-third of people with XLP experience dysgammaglobulinemia, which means they have abnormal levels of some types of antibodies. Antibodies (also known as immunoglobulins) are proteins that attach to specific foreign particles and germs, marking them for destruction. Individuals with dysgammaglobulinemia are prone to recurrent infections.
Cancers of immune system cells (lymphomas) occur in about one-third of people with XLP .
Without treatment, most people with XLP survive only into childhood. Death usually results from hemophagocytic lymphohistiocytosis.
XLP can be divided into two types based on its genetic cause and pattern of signs and symptoms: XLP1 (also known as classic XLP ) and XLP2. People with XLP2 have not been known to develop lymphoma, are more likely to develop hemophagocytic lymphohistiocytosis without EBV infection, usually have an enlarged spleen (splenomegaly), and may also have inflammation of the large intestine (colitis). Some researchers believe that these individuals should actually be considered to have a similar but separate disorder rather than a type of XLP .
XLP1 is estimated to occur in about 1 per million males worldwide. XLP2 is less common, occurring in about 1 per 5 million males.
This condition is generally inherited in an X-linked recessive pattern. The genes associated with this condition are located on the X chromosome. which is one of the two sex chromosomes. In males (who have only one X chromosome ), one altered copy of an associated gene in each cell is sufficient to cause the condition. A characteristic of
X-linked inheritance is that fathers cannot pass X-linked traits to their sons.
In females (who have two X chromosomes), a mutation usually has to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of an associated gene, males are affected by X-linked recessive disorders much more frequently than females. However, in rare cases a female carrying one altered copy of the SH2D1A or XIAP gene in each cell may develop signs and symptoms of this condition.
Diagnosis & Management
These resources address the diagnosis or management of XLP:
These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:
Other Names for This Condition
- Duncan disease
- Epstein-Barr virus-induced lymphoproliferative disease in males
- familial fatal Epstein-Barr infection
- Purtilo syndrome
- severe susceptibility to EBV infection
- severe susceptibility to infectious mononucleosis
- X-linked lymphoproliferative syndrome
Additional Information & Resources
MedlinePlus (5 links)
Genetic and Rare Diseases Information Center (1 link)
Additional NIH Resources (1 link)
Educational Resources (4 links)
Patient Support and Advocacy Resources (3 links)
GeneReviews (1 link)
Genetic Testing Registry (2 links)
ClinicalTrials.gov (1 link)
Scientific articles on PubMed (1 link)
OMIM (2 links)
Sources for This Page
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Latour S. Natural killer T cells and X-linked lymphoproliferative syndrome. Curr Opin Allergy Clin Immunol. 2007 Dec;7(6):510-4. Review.
Marsh RA, Madden L, Kitchen BJ, Mody R, McClimon B, Jordan MB, Bleesing JJ, Zhang K, Filipovich AH. XIAP deficiency: a unique primary immunodeficiency best classified as X-linked familial hemophagocytic lymphohistiocytosis and not as X-linked lymphoproliferative disease. Blood. 2010 Aug 19;116(7):1079-82. doi: 10.1182/blood-2010-01-256099. Epub 2010 May 20.
Marsh RA, Villanueva J, Kim MO, Zhang K, Marmer D, Risma KA, Jordan MB, Bleesing JJ, Filipovich AH. Patients with X-linked lymphoproliferative disease due to BIRC4 mutation have normal invariant natural killer T-cell populations. Clin Immunol. 2009 Jul;132(1):116-23. doi: 10.1016/j.clim.2009.03.517. Epub 2009 Apr 23.
Nagy N, Klein E. Deficiency of the proapoptotic SAP function in X-linked lymphoproliferative disease aggravates Epstein-Barr virus (EBV) induced mononucleosis and promotes lymphoma development. Immunol Lett. 2010 May 4;130(1-2):13-8. doi: 10.1016/j.imlet.2010.01.002. Epub 2010 Jan 18. Review.
Nagy N, Matskova L, Hellman U, Klein G, Klein E. The apoptosis modulating role of SAP (SLAM associated protein) contributes to the symptomatology of the X linked lymphoproliferative disease. Cell Cycle. 2009 Oct 1;8(19):3086-90. Epub 2009 Oct 27.
Rigaud S, Fondan