{"orpha":397596,"name":"Activated PI3K-delta syndrome","type":"Clinical group","group":"Group of disorders","status":"active","flags":[],"synonyms":["APDS","Activated p110-delta syndrome","PASLI","PI3K delta activating mutations causing senescent T cells, lymphadenopathy and immunodeficiency","Senescent T-cells-lymphadenopathy-immunodeficiency syndrome due to p110delta-activating mutation"],"definition":"A rare, genetic, primary immunodeficiency disease characterized by increased susceptibility to recurrent and/or severe bacterial and viral infections (in particular, sinopulmonary bacterial and herpesvirus infections), chronic benign lymphoproliferation (manifesting as lymphadenopathy, hepatosplenomegaly and focal nodular lymphoid hyperplasia), and/or autoimmune disease (including immune cytopenias, juvenile arthritis, glomerulonephritis and sclerosing cholangitis). Immunophenotypically, variable degrees of agammaglobulinemia with increased IgM levels, increased circulating transitional B cells, decreased naïve CD4 and CD8 T-cells with increased CD8 effector/memory T cells are observed.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-397596/","orphanet_url":"https://www.orpha.net/en/disease/detail/397596","names":{"fr":{"name":"Syndrome de PI3K-delta activée","synonyms":["APDS","Syndrome de déficit immunitaire-lymphadénopathie et cellules T sénescentes dus à des mutations activatrices de p110delta","Syndrome de p110-delta activé"],"definition":"Déficit immunitaire primaire rare d'origine génétique, caractérisé par une sensibilité accrue aux infections virales et bactériennes sévères et/ou récurrentes (notamment aux infections par le virus de l'herpès et aux infections bactériennes sinopulmonaires), une lymphoprolifération chronique bénigne (se manifestant par une lymphadénopathie, une hépatosplénomégalie et une hyperplasie nodulaire lymphoïde focale) et/ou une maladie auto-immune (dont des cytopénies immunes, une arthrite juvénile, une glomérulonéphrite et une cholangite sclérosante). Sur le plan du phénotype immunitaire, on observe une agammaglobulinémie de degré variable accompagnée de taux élevés d'IgM et de précurseurs lymphoïdes B circulants, d'une diminution du taux de lymphocytes T CD4<sup>+</sup> et CD8<sup>+</sup> naïfs avec un taux accru de lymphocytes T CD8<sup>+</sup> mémoires/effecteurs."},"de":{"name":"Aktivierendes PIK3-delta-Syndrom","synonyms":["APDS","Aktivierendes p110-Delta-Syndrom","PASLI","Seneszierende T-Zellen, Lymphadenopathie und Immundefizienz durch p110delta-aktivierende Mutationen"]},"es":{"name":"Síndrome de PI3K-delta activado","synonyms":["APDS","PASLI","Síndrome de células-T senescentes-linfadenopatía-inmunodeficiencia por una mutación activadora de PI3K delta","Síndrome de células-T senescentes-linfadenopatía-inmunodeficiencia por una mutación activadora de p110delta","Síndrome de p110-delta activado"],"definition":"Es una inmunodeficiencia primaria genética y poco frecuente caracterizada por una mayor susceptibilidad a infecciones virales y bacterianas graves y/o recurrentes (en particular, infecciones sinopulmonares por bacterias y herpesvirus), linfoproliferación crónica benigna (que se manifiesta como linfadenopatía, hepatoesplenomegalia e hiperplasia nodular linfoide focal) y/o enfermedad autoinmune (incluidas las citopenias inmunes, la artritis juvenil, la glomerulonefritis y la colangitis esclerosante). Inmunofenotípicamente se observan grados variables de agammaglobulinemia con niveles incrementados de IgM, aumento de las células B transicionales circulantes, disminución de las células T CD4 y CD8 naïve con incremento de células T CD8 efectoras / de memoria."},"it":{"name":"Sindrome da attivazione di PI3K-delta","synonyms":["APDS","Immunodeficienza, linfadenopatia e cellule T senescenti dovuti da mutazioni attivanti di p110delta","Sindrome da p110-delta attivata","PASLI","Mutazioni attivanti di PI3K delta associate a cellule T senescenti, linfadenopatia e immunodeficienza"],"definition":"La sindrome da attivazione PI3K-delta è un'immunodeficienza primitiva rara di origine genetica, caratterizzata da suscettibilità alle infezioni batteriche e virali ricorrenti e/o gravi (in particolare infezioni batteriche sinopolmonari e da herpes virus), linfoproliferazione benigna cronica (che esordisce con linfoadenopatia, epatosplenomegalia ed iperplasia nodulare linfoide focale) e/o malattie autoimmuni (citopenie, artrite giovanile, glomerulonefrite e colangite sclerosante). Le analisi immunofenotipiche evidenziano agammaglobulinemia di gravità variabile, associata all'aumento dei livelli di IgM e delle cellule B transizionali circolanti, diminuzione delle cellule T CD8 e CD4 naive e aumento delle cellule T CD8 effettrici/delle memoria."},"nl":{"name":"Geactiveerd PI3K-delta-syndroom","synonyms":["APDS","Geactiveerd p110-delta-syndroom","PASLI","PI3K-delta-activerende mutaties die senescente T-cellen, lymfadenopathie en immuundeficiëntie veroorzaken","Senescente T-cellen - lymfadenopathie - immuundeficiëntie-syndroom door p110delta-activerende mutatie"],"definition":"Een zeldzame, genetische, primaire immuundeficiëntie, gekarakteriseerd door verhoogde vatbaarheid voor terugkerende en/of ernstige bacteriële en virale infecties (voornamelijk sinopulmonale bacteriële en herpesvirus-infecties), chronische goedaardige lymfoproliferatie (die zich manifesteert als lymfadenopathie, hepatosplenomegalie en focale nodulaire lymfoïde hyperplasie), en/of auto-immuunziekte (waaronder immune cytopenieën, juveniele artritis, glomerulonefritis en scleroserende cholangitis). Immunofenotypisch worden variabele gradaties van agammaglobulinemie met verhoogde IgM-gehaltes, verhoogd aantal circulerende transitionele B-cellen, verminderd aantal naïeve CD4 en CD8 T-cellen met verhoogd aantal CD8 effector/geheugen-T-cellen waargenomen."},"pt":{"name":"Síndrome de activação PIK3 - delta"},"pl":{"name":"Zespół aktywacji PIK3-delta","synonyms":["APDS","Zespół starzejących się komórek T, limfadenopatii i niedoboru odporności spowodowany mutacją aktywności p110delta"]},"cs":{"name":"Syndrom aktivované PI3K-delta","synonyms":["APDS","Syndrom zahrnující stárnoucí T-buňky, lymfadenopatii a imunodeficienci, způsobený mutací aktivovanou p110delta"]},"uk":{"name":"Синдром активованої PI3K-дельта","synonyms":["APDS","Синдром старіння Т-лімфоцитів-лімфаденопатії-імунодефіциту, зумовлений мутацією, що активує p110delta"],"definition":"A rare, genetic, primary immunodeficiency disease characterized by increased susceptibility to recurrent and/or severe bacterial and viral infections (in particular, sinopulmonary bacterial and herpesvirus infections), chronic benign lymphoproliferation (manifesting as lymphadenopathy, hepatosplenomegaly and focal nodular lymphoid hyperplasia), and/or autoimmune disease (including immune cytopenias, juvenile arthritis, glomerulonephritis and sclerosing cholangitis). Immunophenotypically, variable degrees of agammaglobulinemia with increased IgM levels, increased circulating transitional B cells, decreased naïve CD4 and CD8 T-cells with increased CD8 effector/memory T cells are observed."},"zh":{"name":"激活PI3K-δ综合征","synonyms":["P110δ激活突变所致衰老T细胞-淋巴结病-免疫缺陷综合征"],"definition":"本病是一种罕见的遗传性原发性免疫缺陷疾病，其特征是对反复和/或严重的细菌和病毒感染(特别是鼻肺细菌和疱疹病毒感染)、慢性良性淋巴增生(表现为淋巴结节性病变、肝脾肿大和局限性结节性淋巴组织增生)和/或自身免疫性疾病(包括免疫性细胞减少症、青少年关节炎、肾小球肾炎和硬化性胆管炎)的易感性增加。免疫表型表现为不同程度的无丙种球蛋白血症，IgM水平升高，循环过渡性B细胞增多，初始CD4和CD8T细胞减少和CD8效应/记忆T细胞增多。"},"tr":{"name":"Aktif PI3K-delta sendromu","synonyms":["APDS","P110delta'yı aktive eden mutasyona bağlı yaşlanmış T-hücreleri-lenfadenopati-immün yetmezlik sendromu"]}},"xrefs":[{"source":"OMIM","code":"615513","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"616005","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"D81.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0018338","qualifier":"E","icd_relation":null,"validated":true},{"source":"MONDO","code":"18338","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C585640","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C3714976","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"11983","qualifier":"E","icd_relation":null,"validated":true},{"source":"MedDRA","code":"10078281","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98004,"name":"Rare immune disease"},"parents":[{"orpha":696870,"name":"Common variable immunodeficiency phenotype due to germinal monogenic mutation","classifications":[156,195]},{"orpha":717757,"name":"Rare immune disease with inflammatory bowel disease","classifications":[152,156,233]}],"children":[{"orpha":693661,"name":"Activated PI3K-delta syndrome 1","type":"Disease"},{"orpha":693681,"name":"Activated PI3K-delta syndrome 2","type":"Disease"}],"genes":[],"genes_via_subtypes":[],"inheritance":["Autosomal dominant"],"onset":["Adult","Childhood","Infancy"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":250.0,"area":"Worldwide","status":"Validated","source":"34052541[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"Unknown","value":0.0,"area":"Worldwide","status":"Validated","source":"34052541[PMID]_31111319[PMID]_ORPHANET"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2023-01-05","source":"27555459[PMID]_27116393[PMID]","terms":[{"hpo":"HP:0002090","label":"Pneumonia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0200117","label":"Recurrent upper and lower respiratory tract infections","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002960","label":"Autoimmunity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002110","label":"Bronchiectasis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011109","label":"Chronic sinusitis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004313","label":"Decreased circulating antibody level","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0010976","label":"Decreased total B cell count","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002240","label":"Hepatomegaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003496","label":"Increased circulating IgM level","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011956","label":"Intestinal lymphoid nodular hyperplasia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002716","label":"Lymphadenopathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000403","label":"Recurrent otitis media","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001744","label":"Splenomegaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002242","label":"Abnormal intestine morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001369","label":"Arthritis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001508","label":"Failure to thrive","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000365","label":"Hearing impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002665","label":"Lymphoma","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012758","label":"Neurodevelopmental delay","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011110","label":"Recurrent tonsillitis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0031693","label":"Severe Epstein Barr virus infection","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0031692","label":"Severe cytomegalovirus infection","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0032170","label":"Severe varicella zoster infection","frequency":"Occasional (29-5%)","criteria":null}]}}