{"orpha":436252,"name":"Combined immunodeficiency-multiple intestinal atresia","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["CID-MIA/early-onset IBD"],"definition":"A rare genetic disease characterized by multiple intestinal atresia in association with combined immunodeficiency and inflammatory bowel disease. Clinical features include widespread atresia extending from the stomach to the rectum, homogenous calcifications in the abdominal cavity, hepatic cholestasis, cirrhosis, and chronic liver failure, hypoplastic thymus, and increased susceptibility to mainly bacteria and viruses. The immunological phenotype consists of profound generalized T-cell lymphopenia and milder natural killer cell and B-cell lymphopenia, as well as low serum levels of IgG, IgA, and IgM, with elevated serum IgE. The disease is mostly fatal in infancy or childhood.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-436252/","orphanet_url":"https://www.orpha.net/en/disease/detail/436252","names":{"fr":{"name":"Déficit immunitaire combiné-atrésie intestinale multiple","definition":"Maladie génétique rare caractérisée par une atrésie intestinale multiple en association avec une immunodéficience combinée et une maladie inflammatoire de l'intestin. Les signes cliniques sont notamment une atrésie s'étendant de l'estomac au rectum, des calcifications homogènes dans la cavité abdominale, une cholestase hépatique, une cirrhose, une insuffisance hépatique chronique, un thymus hypoplasique et une plus grande sensibilité principalement aux bactéries et aux virus. Le phénotype immunologique consiste en une lymphopénie généralisée sévère des cellules T et une lymphopénie plus légère des cellules NK et des lymphocytes B, ainsi qu'en de faibles taux sériques d'IgG, d'IgA et d'IgM, avec des taux sériques élevés d'IgE. Pendant la petite enfance ou l'enfance, la maladie engage dans la plupart des cas le pronostic vital."},"de":{"name":"Kombinierter Immundefekt mit multipler intestinaler Atresie","synonyms":["CID-MIA/früh beginennde IBD","Immundefekt mit multiplen Darmatresien","TTC7A-Defekt"],"definition":"Eine seltene genetische Erkrankung, die durch multiple Darmatresien in Verbindung mit einem kombinierten Immundefekt und einer entzündlichen Darmerkrankung gekennzeichnet ist. Zu den klinischen Merkmalen gehören weit verbreitete Atresien, die sich vom Magen bis zum Rektum erstrecken, homogene Verkalkungen in der Bauchhöhle, hepatische Cholestase, Zirrhose und chronisches Leberversagen, hypoplastischer Thymus und erhöhte Anfälligkeit für Bakterien und Viren. Der immunologische Phänotyp besteht aus einer ausgeprägten generalisierten T-Zell-Lymphopenie und einer milderen Lymphopenie der natürlichen Killerzellen und der B-Zellen sowie aus niedrigen IgG-, IgA- und IgM-Serumspiegeln mit erhöhtem Serum-IgE. Die Krankheit verläuft im Säuglings- und Kindesalter meist letal."},"es":{"name":"Inmunodeficiencia combinada-atresia intestinal múltiple","synonyms":["CID-MIA/IBD de inicio precoz"],"definition":"Es una enfermedad de base genética poco frecuente caracterizada por atresia intestinal múltiple asociada a inmunodeficiencia combinada y a enfermedad inflamatoria intestinal. Las características clínicas incluyen atresia generalizada que se extiende desde el estómago hasta el recto, calcificaciones homogéneas en la cavidad abdominal, colestasis hepática, cirrosis e insuficiencia hepática crónica, timo hipoplásico y una mayor susceptibilidad, principalmente, a bacterias y virus. El fenotipo inmunológico consiste en grave linfopenia generalizada de células T y más leve de células natural killer y de células B, así como unos niveles séricos bajos de IgG, IgA e IgM y unos niveles séricos elevados de IgE. Por lo general, la enfermedad es letal en la lactancia o en la infancia."},"it":{"name":"Immunodeficienza combinata-atresia intestinale multipla","synonyms":["CID-MIA/IBD a esordio precoce"],"definition":"Si tratta di una malattia genetica rara, caratterizzata da atresia intestinale multipla associata all'immunodeficienza combinata e alla malattia infiammatoria intestinale. I segni clinici comprendono l'atresia diffusa dallo stomaco al retto, le calcificazioni omogenee nella cavità addominale, la colestasi epatica, la cirrosi, l'insufficienza epatica cronica, l'ipoplasia del timo, e la predisposizione alle infezioni batteriche e virali. Il fenotipo immunologico è caratterizzato da una profonda linfopenia generalizzata dei linfociti T, una linfopenia più lieve delle cellule natural killer e dei linfociti B, livelli bassi di IgG, IgA e IgM nel siero, e livelli elevati di IgE nel siero. In genere la malattia è letale durante la prima infanzia o nell'infanzia."},"nl":{"name":"Gecombineerde immuundeficiëntie - multipele darmatresie","synonyms":["CID-MIA/vroeg beginnende IBD"],"definition":"Een zeldzame, genetische aandoening, gekarakteriseerd door multipele intestinale atresie geassocieerd met gecombineerde immuundeficiëntie en inflammatoire darmziekte. Klinische kenmerken zijn onder meer wijdverspreide atresie die zich uitstrekt van maag tot rectum, homogene calcificatie in buikholte, cholestase, cirrose, en chronisch leverfalen, hypoplastische thymus, en verhoogde susceptibiliteit voor voornamelijk bacteriën en virussen. Het immunologische fenotype bestaat uit zeer ernstige gegeneraliseerde lymfopenie van T-cellen en mildere lymfopenie van 'natural killer'-cellen en B-cellen, alsook lage gehaltes van IgG, IgA, en IgM en verhoogd gehalte van IgE in serum. De ziekte is meestal fataal in de zuigelingentijd of kindertijd."},"pt":{"name":"Espectro clínico de imunodeficiência combinada-enteropatia"},"pl":{"name":"Złożony niedobór odporności z wiepoziomową atrezją jelit","synonyms":["CID-MIA/IBD o wczesnym początku"]},"cs":{"name":"Spektrum zahrnující kombinovaný imunodeficit a enteropatii","synonyms":["CID-MIA/IBD s časným nástupem"]},"uk":{"name":"Комбінований імунодефіцит-спектр ентеропатії","synonyms":["CID-MIA / ранній початок IBD"],"definition":"A rare genetic disease characterized by multiple intestinal atresia in association with combined immunodeficiency and inflammatory bowel disease. Clinical features include widespread atresia extending from the stomach to the rectum, homogenous calcifications in the abdominal cavity, hepatic cholestasis, cirrhosis, and chronic liver failure, hypoplastic thymus, and increased susceptibility to mainly bacteria and viruses. The immunological phenotype consists of profound generalized T-cell lymphopenia and milder natural killer cell and B-cell lymphopenia, as well as low serum levels of IgG, IgA, and IgM, with elevated serum IgE. The disease is mostly fatal in infancy or childhood."},"zh":{"name":"联合免疫缺陷病-肠病谱","synonyms":["CID-MIA/早发性 IBD"]},"tr":{"name":"Kombine immün yetmezlik-enteropati spektrumu","synonyms":["CID-MIA/erken başlangıçlı IBD"]}},"xrefs":[{"source":"OMIM","code":"243150","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"619708","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"D81.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"4A01.1Y","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0800030","qualifier":"E","icd_relation":null,"validated":true},{"source":"MONDO","code":"30831","qualifier":"E","icd_relation":null,"validated":true},{"source":"MONDO","code":"800030","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5680044","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":93890,"name":"Rare developmental defect during embryogenesis"},"parents":[{"orpha":506219,"name":"Rare disorder potentially indicated for hematopoietic stem cell transplant","classifications":[233]},{"orpha":717757,"name":"Rare immune disease with inflammatory bowel disease","classifications":[152,156,233]},{"orpha":331217,"name":"Syndrome with combined immunodeficiency","classifications":[156,195]},{"orpha":108969,"name":"Syndromic intestinal malformation","classifications":[147,156,182,233]}],"children":[],"genes":[{"symbol":"TTC7A","name":"tetratricopeptide repeat domain 7A","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"24417819[PMID]_25174867[PMID]","hgnc":"19750","ensembl":"ENSG00000068724","omim":"609332","loci":["2p21"]},{"symbol":"PI4KA","name":"phosphatidylinositol 4-kinase alpha","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"34415310[PMID]","hgnc":"8983","ensembl":"ENSG00000241973","omim":"600286","loci":["22q11.21"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":30.0,"area":"Worldwide","status":"Validated","source":"ORPHANET"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2017-10-18","source":"23423984[PMID]_2240032[PMID]_15137007[PMID]_5091250[PMID]_4752999[PMID]_4470900[PMID]_1250662[PMID]_2240032[PMID]_514679[PMID]_6637476[PMID]_7554349[PMID]","terms":[{"hpo":"HP:0010766","label":"Ectopic calcification","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002589","label":"Gastrointestinal atresia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0011100","label":"Intestinal atresia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0004430","label":"Severe combined immunodeficiency","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003270","label":"Abdominal distention","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002223","label":"Absent eyebrow","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0025085","label":"Bloody diarrhea","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002721","label":"Immunodeficiency","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001511","label":"Intrauterine growth retardation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0005229","label":"Jejunoileal ulceration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001561","label":"Polyhydramnios","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008070","label":"Sparse hair","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100889","label":"Abnormality of the ductus choledochus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002293","label":"Alopecia of scalp","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000778","label":"Hypoplasia of the thymus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002566","label":"Intestinal malrotation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100592","label":"Peritoneal abscess","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005224","label":"Rectal abscess","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002722","label":"Recurrent abscess formation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001072","label":"Thickened skin","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001890","label":"Autoimmune hemolytic anemia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002960","label":"Autoimmunity","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0010959","label":"Congenital pulmonary airway malformation","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000872","label":"Hashimoto thyroiditis","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0012115","label":"Hepatitis","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0008404","label":"Nail dystrophy","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001539","label":"Omphalocele","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0003765","label":"Psoriasiform dermatitis","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0100651","label":"Type I diabetes mellitus","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001629","label":"Ventricular septal defect","frequency":"Very rare (<4-1%)","criteria":null}]}}