Pdf hematopoietic cell transplantation for asymptomatic. The genetic trait is transmitted in an xlinked recessive mode as a result of which it is nearly always fatal to. Features include hemophagocytic lymphohistiocytosis hlh, lymphomas, and dysgammaglobulinemias. Xlinked lymphoproliferative disease xlp, also called duncan disease is a rare disorder that was first identified by purtillo, et al in the duncan family, in which 6 of 18 males died of lymphoproliferative disease, including fulminant infectious mononucleosis fim and lymphoma. Xlinked means that the disorder is due to a mutation in one or more genes on the x sex chromosome. Disease onset is typically in early childhood, and the average life expectancy of affected males is. Variable clinical phenotypes of xlinked lymphoproliferative syndrome in china. How is xlinked lymphoproliferative xlp syndrome treated. Xlinked lymphoproliferative disease xlp has two recognizable subtypes, xlp1 and xlp2. Xlinked lymphoproliferative disease xlp1, described in the mid1970s and molecularly defined in 1998, and xlp2, reported in 2006, are prematurely lethal genetic immunodeficiencies that share susceptibility to overwhelming inflammatory responses to certain infectious triggers. Xlinked lymphoproliferative syndrome symptoms, diagnosis. Onset of the accelerated phase seems to be associated with.
This textbook was necessitated by the broadening recognition of cytokine storm syndromes css and their import and impact on health worldwide. Xlp1 is characterized predominantly by one of three commonly recognized phenotypes. An 18yearold male with xlinked lymphoproliferative. Xlinked lymphoproliferative syndrome xlp is a rare hereditary disease characterized by a violation of the immune response to the epsteinbarr virusebv virus. X linked lymphoproliferative syndrome nord national. Xlinked lymphoproliferative syndrome prehct data xlinked lymphoproliferative syndrome, also known as xlp or duncans syndrome, is a rare inherited immunodeficiency. The xlinked lymphoproliferative syndrome registry was recently established and is funded by the national cancer institute. This lymphoproliferative syndrome is similar to that observed in the chediakhigashi syndrome, familial hemophagocytic lymphohistiocytosis fhl, xlinked lymphoproliferative xlp syndrome and the virusassociated hemophagocytic syndrome 3. Xlinked lymphoproliferative disease xlp xlp, which primarily affects boys, is characterized by a lifelong vulnerability to epsteinbarr virus ebv, a common type of herpes virus. Xlinked lymphoproliferative syndrome xlp is a very rare disorder in which the immune system does not work properly. The symptoms associated with xlp vary from person to person, and even among family members. Department of immunology, and school of medicine, tehran university of medical sciences. An xlinked recessive lymphoproliferative syndrome has been described in several kindreds 307.
Autoimmune lymphoproliferative syndrome alps is an inherited disorder in which the body cannot properly regulate the number of immune system cells lymphocytes. Xlinked lymphoproliferative syndrome presenting as adult. Xlinked lymphoproliferative syndrome results from a tcell and natural killer cell defect and is characterized by an abnormal response to epsteinbarr virus infection, leading to liver failure, immunodeficiency, lymphoma, fatal lymphoproliferative disease, or. Xlinked lymphoproliferative syndrome xlp is an immune system disorder that occurs almost exclusively in males.
It affect approximately two to three males per million. Xlinked lymphoproliferative syndrome xlp is a rare immunodeficiency condition characterized by an extreme vulnerability to epsteinbarr virus ebv infection, frequently resulting in hemophagocytic lymphohistiocytosis hlh or virusassociated hemophagocytic syndrome vahs. Click on the link to view a sample search on this topic. Xlinked lymphoproliferative syndrome xlp is an immune system disorder. Xlinked lymphoproliferative syndrome xlp, or duncans syndrome, is a rare genetic condition where the immune system does not work properly. Xlinked lymphoproliferative xlp syndrome is a rare immunodeficiency disease that is characterized by a predilection for hemophagocytic lymphohistiocytosis, fatal or nearfatal epsteinbarr virus ebv induced infectious mononucleosis in childhood, subsequent hypogammaglobulinemia, and a markedly increased risk of lymphoma or other lymphop. Frontiers xlinked lymphoproliferative disease type 1. Molecular cloning of the causative gene, sh2d1a, has provided insight into the nature of disease, as well as. Lymphoproliferative disorders 29112016 19 xlinked lymphoproliferative disorder the autoimmune lymphoproliferative syndrome alps castleman disease cd posttransplant lymphoproliferative disease ptld 20. Similarly, marsh et al 2010 published a series of young males who presented with hlh and an xiap pathogenic variant, prompting the conclusion that xiap deficiency may be most appropriately classified as an xlinked form of hemophagocytic lymphohistiocytosis rather than an xlinked lymphoproliferative disease. We report the case of an 18yearold male who developed hemophagocytic lymphohistiocytosis hlh with neurologic complications after primary epsteinbarr virus ebv infection and subsequently develope. Affected males who survive the initial ebv infection develop a variable hypogammaglobulinemia, and.
It is characterized by severe immune dysregulation, which generally manifests as an exaggerated immune response to infection. Xlinked lymphoproliferative syndrome xlp is inherited as an xlinked recessive genetic trait. Xlinked lymphoproliferative syndrome registry annals of. Xlinked lymphoproliferative syndrome xlp is a rare primary immunodeficiency disease that can be divided into two types. Pathogenic hemizygous variants in the sh2d1a gene cause xlinked lymphoproliferative xlp syndrome, a rare primary immunodeficiency usually associated with fatal epsteinbarr virus infection. People with xlp have an increased risk of infection because their body cannot properly regulate the number of immune system cells lymphocytes and blood cells. The gene map location of the altered mutated has been tracked to a site at xq25. The immune system is made up of special cells, proteins, tissues and organs, which work together to protect our bodies from the detrimental effects of pathogens, including bacteria, viruses and fungi. Clinical similarities and differences of patients with x. Xlinked lymphoproliferative syndrome genetic and rare.
Xlinked lymphoproliferative sydrome xlp xlinked lymphoproliferative syndrome, also known as xlp or duncans syndrome, is a rare inherited immunodeficiency. Xlinked lymphoproliferative syndrome results from a tcell and natural killer cell defect and is characterized by an abnormal response to epsteinbarr virus infection, leading to liver failure, immunodeficiency, lymphoma, fatal lymphoproliferative disease, or bone marrow aplasia. Ochs, department of pediatrics, university ofmassachusetts. Symptoms of xlinked lymphoproliferative syndrome including medical symptoms and signs of xlinked lymphoproliferative syndrome, alternative diagnoses, misdiagnosis, and correct diagnosis for xlinked lymphoproliferative syndrome signs or xlinked lymphoproliferative syndrome symptoms. From ghr xlinked lymphoproliferative disease xlp is a disorder of the immune system and bloodforming cells that is found almost exclusively in males. In 1974, two groups independently reported an apparent genetic disorder affecting males with a rapidly fatal course following epsteinbarr virus ebv infection 1,2.
Hemophagocytic lymphohistiocytosis is the most common presenting feature. Xlinked lymphoproliferative disease genetics home reference. The greatest risk for children with xlinked lymphoproliferative syndrome seems to be from the epsteinbarr virus, which causes mononucleosis. Xlinked lymphoproliferative xlp syndrome is a rare recessive genetic disorder that can be divided into two types based on its genetic cause and pattern of signs and symptoms. Xlinked lymphoproliferative syndrome is listed as a rare disease by the office of rare diseases ord of the national institutes of health nih. Ebv is a very common virus that eventually infects most humans. Strangely, in boys with xlinked lymphoproliferative disorder, there is an inability to mount an immune response to the epsteinbarr virus ebv, which often leads to death from bone marrow failure, irreversible hepatitis, and malignant lymphoma. Pubmed is a searchable database of medical literature and lists journal articles that discuss xlinked lymphoproliferative syndrome 2.
Accumulation of excess lymphocytes results in enlargement of the lymph nodes lymphadenopathy, the liver hepatomegaly. Xlinked lymphoproliferative syndrome nicklaus children. Children with common variable immunodeficiency cvid are also at a higher risk of developing a lymphoproliferative disorder. We studied immune responses in six males of a wellcharacterized kindred with the xlinked lymphoproliferative syndrome. People with xlp have an increased chance to develop a severe reaction called fulminant infectious mononucleosis fim. Xlinked lymphoproliferative syndrome natural history of the immunodeficiency john l.
Xlinked lymphoproliferative syndrome immune disorders. Sap, the product of the gene mutated in xlinked lymphoproliferative syndrome xlp, consists of a single sh2 domain that has been shown to bind the cytoplasmic tail of the lymphocyte coreceptor slam. Lymphoproliferative syndrome 2, xlinked concept id. The xlinked lymphoproliferative syndrome is characterized by immunodeficiency to epsteinbarr virus ebv manifested by severe or fatal infectious mononucleosis and acquired immunodeficiency.
Xlinked lymphoproliferative syndrome type 1 xlp1 is a rare congenital immunodeficiency disease. Xlinked lymphoproliferative syndrome is a genetic disease in which the immune system does not work as well as it should. Xlinked lymphoproliferative disease xlp was first described in the 1970s as a fatal lymphoproliferative syndrome associated with infection with epsteinbarr virus ebv. Boys with xlinked immunodeficiency syndrome are at a higher risk of mortality associated with epsteinbarr virus infections, and are predisposed to develop a lymphoproliferative disorder or lymphoma. Xlinked lymphoproliferative xlp syndrome is characterized by a high susceptibility to severe infection with ebv. Inappropriate immune response to epsteinbarr virus ebv infection leading to hemophagocytic lymphohistiocytosis hlh or severe mononucleosis. Two genetically distinct forms of the disease are known. Alps is characterized by the production of an abnormally large number of lymphocytes lymphoproliferation. Xlinked lymphoproliferative syndrome is a primary immunodeficiency disorder. Xlinked lymphoproliferative disease xlp is a disorder of the immune system and bloodforming cells that is found almost exclusively in males. Xlinked lymphoproliferative syndrome 2 genetic and rare. Xiap deficiency is characterized by a key triad of clinical manisfestations, which consist of a high susceptibility to develop.
Xlinked lymphoproliferative syndrome pubmed central pmc. More than half of individuals with this disorder experience an exaggerated immune response to the epsteinbarr virus ebv. Xlinked lymphoproliferative syndrome xlinked lymphoproliferative syndrome nelson, d. Clinical and molecular characteristics of chinese patients. We invite referrals of possible cases of the xlinked lymphoproliferative syndrome as well as unusual. Xlinked lymphoproliferative syndrome xlp, an extremely rare inherited disorder, is characterized by a range of symptoms and findings that occur due to a defective immune system response to infection with the epsteinbarr virus ebv. This means that xlinked lymphoproliferative syndrome, or a subtype of xlinked lymphoproliferative syndrome, affects less than 200,000 people in the us population. Xlinked lymphoproliferative syndrome registry jama. Sap deficiency xlp1 and xiap deficiency xlp2, caused by mutations in. The diagnosis of xlinked lymphoproliferative syndrome xlp should be suspected in males with fulminant epsteinbarr virus ebv induced mononucleosis which may be accompanied by hemophagocytosis. Instructions for xlinked lymphoproliferative syndrome. In most cases, development of lymphoproliferative disease reflects inability to contain infection with ebv. Other patients develop fulminant infectious mononucleosis following infection with ebv.