{"orpha":331206,"name":"T-B-NK+ severe combined immunodeficiency due to complete RAG1/2 deficiency","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["T-B-NK+ SCID due to complete RAG1/2 deficiency"],"definition":"Severe combined immunodeficiency due to complete RAG1/2 deficiency is a rare, genetic T-B- severe combined immunodeficiency disorder due to null mutations in recombination activating gene (RAG) 1 and/or RAG2 resulting in less than 1% of wild type V(D)J recombination activity. Patients present with neonatal onset of life-threatening, severe, recurrent infections by opportunistic fungal, viral and bacterial micro-organisms, as well as skin rashes, chronic diarrhea, failure to thrive and fever. Immunologic observations include profound T- and B-cell lymphopenia, normal NK counts and low or absent serum immunoglobulins; some patients may have eosinophilia.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-331206/","orphanet_url":"https://www.orpha.net/en/disease/detail/331206","names":{"fr":{"name":"Déficit immunitaire combiné sévère T-B-NK+ par déficit complet en RAG1/2","synonyms":["DICS T-B-NK+ par déficit complet en RAG1/2","IDCS T-B-NK+ par déficit complet en RAG1/2","Immunodéficience combinée sévère T-B-NK+ par déficit complet en RAG1/2","SCID T-B-NK+ par déficit complet en RAG1/2"],"definition":"Un déficit génétique immunitaire combiné sévère rare, T-B-, causé par des mutations nulles au niveau du gène activant la recombinaison <i>RAG1</i> et/ou <i>RAG 2</i>, ce qui conduit à moins de 1% d'activité de recombinaison V(D)J de type sauvage. Les patients présentent des infections récurrentes et sévères par des micro-organismes fongiques, bactériens et viraux pendant la période néonatale, mettant en jeu leur pronostic vital, ainsi que des éruptions cutanées, une diarrhée chronique, un retard de croissance staturo-pondérale et une fièvre. Les observations immunologiques incluent une lymphopénie B et T profonde, une numération normale en lymphocytes <i>natural killers</i>, ainsi qu'un faible taux ou une absence d'immunoglobulines. Certains patients peuvent présenter une éosinophilie."},"de":{"name":"Immundefekt, kombinierter schwerer, T-B-NK+, durch kompletten RAG1/2-Mangel","synonyms":["T-B-NK+ SCID durch komplette RAG1/2-Defizienz"],"definition":"Eine seltener kombinierter T- und B-Zell-Immundefekt aufgrund von Null-Mutationen im rekombinationsaktivierenden Gen <i>RAG 1</i> und/oder <i>RAG2</i>, die zu weniger als 1 % der Wildtyp-V(D)J-Rekombinationsaktivität führen. Die Patienten präsentieren sich mit lebensbedrohlichen, schweren, rezidivierenden Infektionen durch opportunistische Pilz-, Virus- und bakterielle Mikroorganismen sowie Hautausschlägen, chronischem Durchfall, Gedeihstörung und Fieber nach der Geburt. Zu den immunologischen Beobachtungen gehören eine ausgeprägte T- und B-Zell-Lymphopenie, normale NK-Zahlen und niedrige oder fehlende Serum-Immunglobuline; einige Patienten können eine Eosinophilie aufweisen."},"es":{"name":"Inmunodeficiencia combinada grave T-B-NK+ por deficiencia completa de RAG1/2","synonyms":["SCID T-B-NK+ por deficiencia completa de RAG1/2","IDCG T-B-NK+ por deficiencia completa de RAG1/2"],"definition":"La inmunodeficiencia combinada grave por deficiencia completa de RAG1/2 es un trastorno genético de inmunodeficiencia combinada grave T-B poco frecuente, debido a mutaciones nulas en el gen activador de la recombinación (RAG) 1 y /o RAG2, que resulta en menos del 1% de la actividad recombinante normal de la región V (D) J. Los afectados presentan infecciones graves, recurrentes y potencialmente mortales, de inicio neonatal, por hongos oportunistas y microorganismos virales y bacterianos, así como erupciones cutáneas, diarrea crónica, fallo de medro y fiebre. Los trastornos inmunológicos incluyen linfopenia profunda de células T y B, recuentos normales de células NK e inmunoglobulinas séricas bajas o ausentes; algunos afectados pueden presentar eosinofilia."},"it":{"name":"Immunodeficienza combinata grave T-B-NK+ da deficit completo di RAG1/2","synonyms":["SCID T-B-NK+ da deficit completo di RAG1/2"],"definition":"L'immunodeficienza combinata grave da deficit completo di RAG1/2 è un'immunodeficienza combinata grave T-B- rara di origine genetica, causata da mutazioni null nel gene attivante la ricombinazione (RAG) 1 e/o RAG2, che porta a meno dell'1% l'attività ricombinante V(D)J wild type. I pazienti presentano infezioni neonatali ricorrenti gravi e potenzialmente letali da funghi, virus e microorganismi batterici opportunistici, eruzioni cutanee, diarrea cronica, ritardo della crescita e febbre. Dal punto di vista immunologico, si osservano la linfopenia delle cellule T e B, un numero normale di NK e livelli nulli o bassi di immunoglobuline nel siero. Alcuni pazienti presentano eosinofilia."},"nl":{"name":"T-B-NK+ ernstige gecombineerde immuundeficiëntie door volledige RAG1/2-deficiëntie","synonyms":["T-B-NK+ SCID door volledige RAG1/2-deficiëntie"],"definition":"Ernstige gecombineerde immuundeficiëntie door volledige RAG1/2-deficiëntie is een zeldzame, genetische T-B- ernstige gecombineerde immuundeficiëntie als gevolg van nulmutaties in recombinatie-activerend gen (RAG) 1 en/of RAG2, wat leidt tot minder dan 1% van de wild-type V(D)J-recombinatie-activiteit. Patiënten vertonen neonatale aanvang van levensbedreigende, ernstige, terugkerende infecties door opportunistische schimmels, en virale en bacteriële micro-organismen, alsook huiduitslag, chronische diarree, groeiachterstand en koorts. Immunologische waarnemingen zijn onder meer zeer ernstige lymfopenie van T- en B-cellen, normale aantallen NK-cellen en weinig of geen immunoglobulinen in het serum; sommige patiënten hebben mogelijk eosinofilie."},"pt":{"name":"Imunodeficiência grave combinada por défice completo de RAG1/2"},"pl":{"name":"Ciężki złożony Niedobór odporności z powodu całkowitego deficytu RAG1/2","synonyms":["SCID z powodu całkowitego niedoboru RAG1/2"]},"cs":{"name":"Těžká kombinovaná imunodeficience způsobená kompletním RAG1/2 deficitem","synonyms":["SCID způsobená kompletním RAG1/2 deficitem"]},"uk":{"name":"Тяжкий комбінований імунодефіцит, зумовлений повною недостатністю RAG1/2","synonyms":["SCID через повну недостатність RAG1/2"],"definition":"Severe combined immunodeficiency due to complete RAG1/2 deficiency is a rare, genetic T-B- severe combined immunodeficiency disorder due to null mutations in recombination activating gene (RAG) 1 and/or RAG2 resulting in less than 1% of wild type V(D)J recombination activity. Patients present with neonatal onset of life-threatening, severe, recurrent infections by opportunistic fungal, viral and bacterial micro-organisms, as well as skin rashes, chronic diarrhea, failure to thrive and fever. Immunologic observations include profound T- and B-cell lymphopenia, normal NK counts and low or absent serum immunoglobulins; some patients may have eosinophilia."},"zh":{"name":"完全性RAG1/2基因缺乏所致严重联合免疫缺陷","synonyms":["完全性RAG1/2基因缺乏所致SCID"],"definition":"RAG1/2基因完全缺乏所致重症联合免疫缺陷是一种罕见的遗传性T-B-重症联合免疫缺陷疾病，其原因是重组激活基因（RAG）1和/或RAG2的零突变导致野生型V（D）J重组活性低于1%。患者表现为新生儿起病的危及生命的严重、反复机会性真菌、病毒和细菌感染，以及皮疹、慢性腹泻、生长发育迟滞和发烧。免疫学表现包括严重的T细胞和B细胞淋巴细胞减少，正常NK计数和血清免疫球蛋白低或缺乏；一些患者可能有嗜酸性粒细胞增多症。"},"tr":{"name":"Tam RAG1/2 eksikliğine bağlı ağır kombine immün yetmezlik","synonyms":["Tam RAG1/2 eksikliğine bağlı SCID"]}},"xrefs":[{"source":"OMIM","code":"601457","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"D81.1","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0011086","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4707355","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"10339","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98004,"name":"Rare immune disease"},"parents":[{"orpha":720314,"name":"T-B-NK+ severe combined immunodeficiency without microcephaly","classifications":[156,195,233]}],"children":[],"genes":[{"symbol":"RAG1","name":"recombination activating 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"8810255[PMID]","hgnc":"9831","ensembl":"ENSG00000166349","omim":"179615","loci":["11p12"]},{"symbol":"RAG2","name":"recombination activating 2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"8810255[PMID]","hgnc":"9832","ensembl":"ENSG00000175097","omim":"179616","loci":["11p12"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy"],"prevalence":[{"type":"Point prevalence","qualification":"Value and class","class":"1-9 / 100 000","value":1.0,"area":"Europe","status":"Validated","source":"European Medicines Agency 2014[OTHER]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-10-23","source":"11133745[PMID]_16276422[PMID]_19458910[PMID]_24481607[PMID]","terms":[{"hpo":"HP:0010975","label":"Abnormal B cell count","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0011839","label":"Abnormal T cell count","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002720","label":"Decreased circulating IgA level","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0004315","label":"Decreased circulating IgG level","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0004313","label":"Decreased circulating antibody level","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002850","label":"Decreased circulating total IgM","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0031381","label":"Decreased lymphocyte proliferation in response to mitogen","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0045080","label":"Decreased proportion of CD3-positive T cells","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001508","label":"Failure to thrive","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001945","label":"Fever","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001888","label":"Lymphopenia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004385","label":"Protracted diarrhea","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002718","label":"Recurrent bacterial infections","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002743","label":"Recurrent enteroviral infections","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002841","label":"Recurrent fungal infections","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0200117","label":"Recurrent upper and lower respiratory tract infections","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004429","label":"Recurrent viral infections","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0031402","label":"Reduced antigen-specific T cell proliferation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0040089","label":"Abnormal natural killer cell count","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001890","label":"Autoimmune hemolytic anemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002960","label":"Autoimmunity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002910","label":"Elevated circulating hepatic transaminase concentration","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002240","label":"Hepatomegaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001433","label":"Hepatosplenomegaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001880","label":"Increased total eosinophil count","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002840","label":"Lymphadenitis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000980","label":"Pallor","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000988","label":"Skin rash","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001873","label":"Thrombocytopenia","frequency":"Occasional (29-5%)","criteria":null}]}}