{"orpha":538934,"name":"X-linked lymphoproliferative disease due to XIAP deficiency","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["XIAP deficiency syndrome","XLP2","X-linked lymphoproliferative syndrome type 2"],"definition":"A rare, genetic, primary immunodeficiency disorder characterized by an abnormal immune response to Epstein-Barr virus (EBV) infection, caused by hemizygous mutations in the X-linked <i>XIAP</i> gene, resulting in B cell lymphoproliferation and manifesting with various phenotypes which include EBV-driven hemophagocytic lymphohistiocytosis, hypogammaglobulinemia, recurrent splenomegaly, hepatitis, colitis, and intestinal bowel disease with features of Crohn's disease. Additional manifestations include variable auto-inflammatory symptoms such as uveitis, arthritis, skin abscesses, erythema nodosum, and nephritis. Neurological involvement is rare and lymphoma is never observed. Laboratory findings include normal or increased activated T cells, low or normal iNKT cells, and normal or reduced memory B cells.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-538934/","orphanet_url":"https://www.orpha.net/en/disease/detail/538934","names":{"fr":{"name":"Maladie lymphoproliférative liée à l'X par déficit en XIAP","synonyms":["Maladie lymphoproliférative liée à l'X type 2","Syndrome lymphoprolifératif lié à l'X type 2","XLP2"],"definition":"Déficit immunitaire primaire rare d'origine génétique caractérisé par une réponse immunitaire anormale à une infection par le virus d'Epstein-Barr (EBV), dû à des mutations hémizygotes du gène <i>XIAP</i> lié à l'X, à l'origine d'une prolifération de lymphocytes B et se manifestant par divers phénotypes dont une lymphohistiocytose hémophagocytaire à virus EBV, une hypogammaglobulinémie, une splénomégalie récurrente, une hépatite, une colite et une maladie inflammatoire chronique de l'intestin avec des manifestations de maladie de Crohn. Les autres manifestations comprennent des symptômes auto-inflammatoires variables, tels qu'une uvéite, une arthrite, des abcès cutanés, un érythème noueux et une néphrite. Les atteintes neurologiques sont rares et aucun cas de lymphome n'a été rapporté. Les analyses biologiques mettent en évidence un taux normal ou accru de lymphocytes T activés, un taux normal ou faible de cellules iNKT et un taux normal ou réduit de lymphocytes B à mémoire."},"de":{"name":"X-chromosomales lymphoproliferatives Syndrom durch XIAP-Mangel","synonyms":["X-chromosomales lymphoproliferatives Syndrom Typ 2","XIAP-Defizienz-Syndrom","XIAP-Mangel-Syndrom","XLP2"],"definition":"Eine seltener, genetisch bedingter primärer Immundefekt, der durch eine gestörte Immunantwort auf eine Infektion mit dem Epstein-Barr-Virus (EBV) gekennzeichnet ist. Ursächlich sind hemizygote Mutationen im X-chromosomalen <i>XIAP</i>-Gen, die zu einer Lymphoproliferation der B-Zellen führen und variable Phänotypen verursachen. Das Syndrom kann sich mit einer EBV-bedingte hämophagozytische Lymphohistiozytose, Hypogammaglobulinämie, rezidivierender Splenomegalie, Hepatitis, Kolitis und Darmerkrankungen mit Merkmalen von Morbus Crohn manifestieren. Weitere Merkmale sind variable autoinflammatorische Symptome wie Uveitis, Arthritis, Hautabszesse, Erythema nodosum und Nephritis. Eine neurologische Beteiligung ist selten und ein Lymphom wird nie beobachtet. Zu den Laborbefunden gehören normale oder erhöhte aktivierte T-Zellen, reduzierte oder normale Anzahl der iNKT-Zellen und normale oder verringerte Anzahl an B-Gedächtniszellen."},"es":{"name":"Enfermedad linfoproliferativa ligada al cromosoma X por deficiencia de XIAP","synonyms":["Síndrome de deficiencia de XIAP","Síndrome linfoproliferativo ligado al X tipo 2","XLP2"],"definition":"Es una inmunodeficiencia primaria genética y poco frecuente caracterizada por una respuesta inmunológica anómala a la infección por el virus de Epstein-Barr (VEB), causada por mutaciones en homocigosis en el gen <i>XIAP</i> ligado al cromosoma X. Dicha alteración resulta en linfoproliferación de células B que se manifiesta con varios fenotipos que incluyen la linfohistiocitosis hemofagocítica causada por EBV, hipogammaglobulinemia, esplenomegalia recurrente, hepatitis, colitis y enfermedad intestinal inflamatoria con características de la enfermedad de Crohn. Otras manifestaciones adicionales incluyen síntomas autoinflamatorios variables como uveítis, artritis, abscesos cutáneos, eritema nodoso y nefritis. La afectación neurológica es infrecuente y nunca se observa linfoma. Los hallazgos de laboratorio incluyen niveles normales o aumentados de células T activadas, niveles normales o reducidos de células NKTi y niveles normales o reducidos de células B de memoria."},"it":{"name":"Malattia linfoproliferativa legata all'X da deficit di XIAP","definition":"Si tratta di un'immunodeficienza primitiva genetica rara, caratterizzata da una risposta immunitaria anomala all'infezione da virus di Epstein-Barr (EBV), causata da mutazioni emizigoti nel gene <i>XIAP</i> correlato all'X, che esitano nella proliferazione dei linfociti B. La malattia esordisce con diversi fenotipi, che comprendono la linfoistiocitosi emofagocitica indotta da EBV, l'ipogammaglobulinemia, la splenomegalia ricorrente, l'epatite, la colite e la malattia intestinale con i segni clinici della malattia di Crohn. La malattia di associa anche a sintomi autoinfiammatori di gravità variabile, come l'uveite, l'artrite, gli ascessi cutanei, l'eritema nodoso e la nefrite. È raro l'interessamento neurologico. Non si associa mai al linfoma. Gli esami di laboratorio evidenziano un numero normale o aumentato di cellule T attivate, un numero ridotto o normale di cellule iNKT, e un numero normale o ridotto di linfociti B della memoria."},"nl":{"name":"X-gebonden lymfoproliferatieve ziekte door XIAP-deficiëntie","synonyms":["X-gebonden lymfoproliferatief syndroom type 2","XIAP-deficiëntiesyndroom","XLP2"],"definition":"Een zeldzame, genetische, primaire immuundeficiëntie die gekarakteriseerd wordt door een abnormale immuunrespons op infectie met Epstein-Barrvirus (EBV), die veroorzaakt wordt door hemizygote mutaties in het X-gebonden gen <i>XIAP</i> wat leidt tot lymfoproliferatie van B-cellen, en die zich manifesteert met verschillende fenotypes waaronder door EBV veroorzaakte hemofagocytaire lymfohistiocytose, hypogammaglobulinemie, recurrente splenomegalie, hepatitis, colitis, en darmziekte met kenmerken van ziekte van Crohn. Bijkomende manifestaties zijn onder meer variabele auto-inflammatoire symptomen zoals uveïtis, artritis, huidabcessen, erythema nodosum, en nefritis. Neurologische betrokkenheid is zeldzaam en lymfoom wordt nooit waargenomen. Laboratoriumbevindingen omvatten normaal of verhoogd aantal geactiveerde T-cellen, laag of normaal aantal iNKT-cellen, en normaal of verlaagd aantal B-geheugencellen."},"pt":{"name":"Doença linfoproliferativa ligada ao X por deficiência de XIAP","definition":"Doença genética, rara, de imunodeficiência primária caracterizada por uma resposta imune anómala à infeção pelo vírus Epstein-Barr (EBV), causada por mutações hemizigóticas no gene XIAP ligado ao X, resultando em linfoproliferação de células B e manifestando-se sob a forma de vários fenótipos que incluem EBV-linfohistiocitose hemofagocítica, hipogamaglobulinemia, esplenomegalia recorrente, hepatite, colite e doença intestinal com características da doença de Crohn. Manifestações clínicas adicionais incluem sintomas auto-inflamatórios variáveis, como uveíte, artrite, abscessos cutâneos, eritema nodoso e nefrite. O envolvimento neurológico é raro e o linfoma não ocorre. Os achados laboratoriais incluem células T ativadas (normal ou com níveis elevados), células iNKT baixas ou normais e células B de memória normais ou reduzidas."},"pl":{"name":"Choroba limfoproliferacyjna sprzężona z chromosomem X spowodowana niedoborem XIAP","synonyms":["XIAP deficiency syndrome","XLP2","X-linked lymphoproliferative syndrome type 2"]},"cs":{"name":"X-vázané lymfoproliferativní onemocnění způsobené deficitem XIAP","synonyms":["XLP2","XIAP deficit","X-vázaný lymfoproliferativní syndrom, typ 2"]},"uk":{"name":"Х-зчеплене лімфопроліферативне захворювання, зумовлене дефіцитом XIAP","synonyms":["Синдром дефіциту XIAP","Х-зчеплений лімфопроліферативний синдром, тип 2","XLP2"],"definition":"A rare, genetic, primary immunodeficiency disorder characterized by an abnormal immune response to Epstein-Barr virus (EBV) infection, caused by hemizygous mutations in the X-linked <i>XIAP</i> gene, resulting in B cell lymphoproliferation and manifestating with various phenotypes which include EBV-driven hemophagocytic lymphohistiocytosis, hypogammaglobulinemia, recurrent splenomegaly, hepatitis, colitis, and intestinal bowel disease with features of Crohn's disease. Additional manifestations include variable auto-inflammatory symptoms such as uveitis, arthritis, skin abscesses, erythema nodosum, and nephritis. Neurological involvement is rare and lymphoma is never observed. Laboratory findings include normal or increased activated T cells, low or normal iNKT cells, and normal or reduced memory B cells."},"zh":{"name":"XIAP基因缺陷诱导的X连锁淋巴组织增生性疾病","synonyms":["X连锁淋巴组织增生综合征2型"],"definition":"一种罕见遗传性原发性免疫缺陷病，其特征是对EB病毒（EBV）感染的异常免疫反应，由X染色体连锁 XIAP基因的半合子突变引起。导致B细胞淋巴增生，并表现为各种表型，包括EBV驱动的嗜血细胞性淋巴组织细胞增多症、高丙种球蛋白血症、复发性脾肿大、肝炎、结肠炎和具有克罗恩病特征的肠道疾病。其他表现包括多种自身炎症症状，如葡萄膜炎、关节炎、皮肤脓肿、结节性红斑和肾炎等。神经系统受累罕见，无淋巴瘤。实验室检查结果包括活化T细胞正常或增加，iNKT细胞低或正常，记忆B细胞正常或减少。"},"tr":{"name":"XIAP eksikliğine bağlı X'e bağlı lenfoproliferatif hastalık","synonyms":["XLP2","XIAP eksikiği sendromu","X'e bağlı lenfoproliferatif sendrom tip 2"]}},"xrefs":[{"source":"OMIM","code":"300635","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"D82.3","qualifier":"NTBT","icd_relation":"inclusion","validated":true},{"source":"ICD-11","code":"4A01.22","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"2118404242"},{"source":"MONDO","code":"0010385","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C564469","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C1845076","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"10916","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98004,"name":"Rare immune disease"},"parents":[{"orpha":717757,"name":"Rare immune disease with inflammatory bowel disease","classifications":[152,156,233]},{"orpha":2442,"name":"X-linked lymphoproliferative disease","classifications":[156,195]}],"children":[],"genes":[{"symbol":"XIAP","name":"X-linked inhibitor of apoptosis","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301580[PMID]","hgnc":"592","ensembl":"ENSG00000101966","omim":"300079","loci":["Xq25"]}],"genes_via_subtypes":[],"inheritance":["X-linked recessive"],"onset":["Adolescent","Adult","Childhood","Infancy"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":100.0,"area":"Worldwide","status":"Validated","source":"29942301[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_29942301[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2024-05-16","source":"20301580[PMID]_25666262[PMID]_25737324[PMID]_24942515[PMID]_21119115[PMID]","terms":[{"hpo":"HP:0002721","label":"Immunodeficiency","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0100280","label":"Crohn's disease","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012115","label":"Hepatitis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0005229","label":"Jejunoileal ulceration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001876","label":"Pancytopenia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001954","label":"Recurrent fever","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0034799","label":"Splenic hemophagocytosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001744","label":"Splenomegaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001369","label":"Arthritis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030151","label":"Cholangitis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002583","label":"Colitis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0031292","label":"Cutaneous abscess","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004313","label":"Decreased circulating antibody level","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012219","label":"Erythema nodosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002037","label":"Inflammation of the large intestine","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000123","label":"Nephritis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002719","label":"Recurrent infections","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0040218","label":"Reduced natural killer cell count","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000083","label":"Renal insufficiency","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0031693","label":"Severe Epstein Barr virus infection","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000554","label":"Uveitis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001399","label":"Hepatic failure","frequency":"Very rare (<4-1%)","criteria":null}]}}