{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T02:16:43Z","timestamp":1793067403178,"version":"4.5.0"},"reference-count":14,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T00:00:00Z","timestamp":1745884800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T00:00:00Z","timestamp":1745884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Allergy Asthma Clin Immunol"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>X-linked inhibitor of apoptosis (XIAP) deficiency is a rare inborn error of immunity which occurs secondary to mutations in the XIAP\/BIRC4 gene. Disease onset usually manifests within the first few years of life, and is associated with a spectrum of clinical features, secondary to immune dysregulation. Males typically present with refractory chronic colitis, hemophagocytic lymphohistiocytosis, and severe and\/or recurrent infections. Laboratory analysis may reveal hypogammaglobulinemia and cytopenias. At present, the only curative treatment is allogenic hematopoietic stem cell transplantation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Case presentation<\/jats:title>\n            <jats:p>A 24-year-old gentleman, immigrant from the Democratic Republic of Congo, was referred to outpatient immunology for evaluation of an inborn error of immunity given a past medical history significant for refractory fistulizing Crohn\u2019s disease, arthritis, liver abscesses, prior disseminated tuberculosis, anemia, and recurrent infections. He had been asymptomatic throughout his childhood and adolescence, with no infections or symptoms of inflammatory disease until the age of 19, when he was diagnosed with Crohn\u2019s disease. He was soon after admitted to hospital and was diagnosed with hemophagocytic lymphohistiocytosis. Primary immunodeficiency gene panel testing revealed a nonsense variant XIAP c833C\u2009&gt;\u2009G p.(Ser278*), which generates a premature stop codon at exon 2 (of total 7 exons). On flow cytometry analysis, XIAP protein expression was significantly reduced, confirming the diagnosis of XIAP deficiency.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>This is one of the only documented reports of a patient with XIAP deficiency, presenting with symptom-onset in adulthood. This case highlights the need to maintain a high index of suspicion for XIAP deficiency in patients with the appropriate clinical presentation, despite advanced age of presentation.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13223-025-00965-4","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T16:28:49Z","timestamp":1745944129000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Late presentation of X-linked inhibitor of apoptosis (XIAP) deficiency in a young adult"],"prefix":"10.1186","volume":"21","author":[{"given":"Samina","family":"Nazarali","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"Derfalvi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Clark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,29]]},"reference":[{"issue":"1","key":"965_CR1","doi-asserted-by":"publisher","first-page":"5","DOI":"10.7453\/gahmj.2012.1.1.001","volume":"1","author":"D Riley","year":"2012","unstructured":"Riley D, Hao JJ, Kiene H, Kienle G, Mittelman M, Plotnikoff GA. The CARE guidelines: consensus-based clinical case reporting guideline development. Glob Adv Health Med. 2012;1(1):5\u20136.","journal-title":"Glob Adv Health Med"},{"issue":"7115","key":"965_CR2","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1038\/nature05257","volume":"444","author":"S Rigaud","year":"2006","unstructured":"Rigaud S, Fondan\u00e8che MC, Lambert N, Pasquier B, Mateo V, Soulas P, et al. XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome. Nature. 2006;444(7115):110\u20134.","journal-title":"Nature"},{"issue":"10","key":"965_CR3","doi-asserted-by":"publisher","first-page":"988","DOI":"10.1038\/sj.embor.7400795","volume":"7","author":"BP Eckelman","year":"2006","unstructured":"Eckelman BP, Salvesen GS, Scott FL. Human inhibitor of apoptosis proteins: why XIAP is the black sheep of the family. EMBO Rep. 2006;7(10):988\u201394.","journal-title":"EMBO Rep"},{"key":"965_CR4","doi-asserted-by":"publisher","first-page":"660520","DOI":"10.3389\/fped.2021.660520","volume":"9","author":"ACA Mudde","year":"2021","unstructured":"Mudde ACA, Booth C, Marsh RA. Evolution of our understanding of XIAP deficiency. Front Pediatr. 2021;9:660520.","journal-title":"Front Pediatr"},{"issue":"6","key":"965_CR5","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1016\/j.immuni.2009.04.011","volume":"30","author":"MJM Bertrand","year":"2009","unstructured":"Bertrand MJM, Doiron K, Labb\u00e9 K, Korneluk RG, Barker PA, Saleh M. Cellular inhibitors of apoptosis cIAP1 and cIAP2 are required for innate immunity signaling by the pattern recognition receptors NOD1 and NOD2. Immunity. 2009;30(6):789\u2013801.","journal-title":"Immunity"},{"key":"965_CR6","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.semcdb.2015.01.015","volume":"39","author":"S Latour","year":"2015","unstructured":"Latour S, Aguilar C. XIAP deficiency syndrome in humans. Semin Cell Dev Biol. 2015;39:115\u201323.","journal-title":"Semin Cell Dev Biol"},{"issue":"18","key":"965_CR7","doi-asserted-by":"publisher","first-page":"2847","DOI":"10.1182\/blood-2014-03-564609","volume":"124","author":"WC Hsieh","year":"2014","unstructured":"Hsieh WC, Chuang YT, Chiang IH, Hsu SC, Miaw SC, Lai MZ. Inability to resolve specific infection generates innate immunodeficiency syndrome in Xiap-\/- mice. Blood. 2014;124(18):2847\u201357.","journal-title":"Blood"},{"issue":"6","key":"965_CR8","doi-asserted-by":"publisher","first-page":"1796","DOI":"10.1016\/j.celrep.2014.05.008","volume":"7","author":"M Yabal","year":"2014","unstructured":"Yabal M, M\u00fcller N, Adler H, Knies N, Gro\u00df CJ, Damgaard RB, et al. XIAP restricts TNF- and RIP3-dependent cell death and inflammasome activation. Cell Rep. 2014;7(6):1796\u2013808.","journal-title":"Cell Rep"},{"issue":"4","key":"965_CR9","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1007\/s10875-015-0141-9","volume":"35","author":"C Aguilar","year":"2015","unstructured":"Aguilar C, Latour S. X-linked inhibitor of apoptosis protein deficiency: more than an X-linked lymphoproliferative syndrome. J Clin Immunol. 2015;35(4):331\u20138.","journal-title":"J Clin Immunol"},{"issue":"3","key":"965_CR10","doi-asserted-by":"publisher","first-page":"e102","DOI":"10.1097\/PG9.0000000000000102","volume":"2","author":"SA Zacharias","year":"2021","unstructured":"Zacharias SA, Seshadri P, Hwang S, Baker L, Powell J, del Fernando J, et al. Delayed diagnosis of X-linked lymphoproliferative syndrome type 2 in a 17-year-old male with severe Crohn\u2019s disease and recurrent skin infections. JPGN Rep. 2021;2(3):e102.","journal-title":"JPGN Rep"},{"issue":"1","key":"965_CR11","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.clim.2013.07.004","volume":"149","author":"C Speckmann","year":"2013","unstructured":"Speckmann C, Lehmberg K, Albert MH, Damgaard RB, Fritsch M, Gyrd-Hansen M, et al. X-linked inhibitor of apoptosis (XIAP) deficiency: the spectrum of presenting manifestations beyond hemophagocytic lymphohistiocytosis. Clin Immunol. 2013;149(1):133\u201341.","journal-title":"Clin Immunol"},{"issue":"2","key":"965_CR12","first-page":"456","volume":"150","author":"L Yang","year":"2022","unstructured":"Yang L, Booth C, Speckmann C, Seidel MG, Worth AJJ, Kindle G, et al. Phenotype, genotype, treatment, and survival outcomes in patients with X-linked inhibitor of apoptosis deficiency. JACI. 2022;150(2):456\u201366.","journal-title":"JACI"},{"key":"965_CR13","doi-asserted-by":"publisher","first-page":"735796","DOI":"10.3389\/fmed.2021.735796","volume":"8","author":"A Bichon","year":"2021","unstructured":"Bichon A, Bourenne J, Allardet-Servent J, Papazian L, Hraiech S, Guervilly C, et al. High mortality of HLH in ICU regardless etiology or treatment. Front Med. 2021;8:735796.","journal-title":"Front Med"},{"issue":"1","key":"965_CR14","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1007\/s10875-021-01103-6","volume":"42","author":"DE Arnold","year":"2022","unstructured":"Arnold DE, Nofal R, Wakefield C, Lehmberg K, Wustrau K, Albert MH, et al. Reduced-intensity\/reduced-toxicity conditioning approaches are tolerated in XIAP deficiency but patients fare poorly with acute GVHD. J Clin Immunol. 2022;42(1):36\u201345.","journal-title":"J Clin Immunol"}],"container-title":["Allergy, Asthma &amp; Clinical Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13223-025-00965-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13223-025-00965-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13223-025-00965-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T16:28:50Z","timestamp":1745944130000},"score":1,"resource":{"primary":{"URL":"https:\/\/aacijournal.biomedcentral.com\/articles\/10.1186\/s13223-025-00965-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,29]]},"references-count":14,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["965"],"URL":"https:\/\/doi.org\/10.1186\/s13223-025-00965-4","relation":{},"ISSN":["1710-1492"],"issn-type":[{"value":"1710-1492","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,29]]},"assertion":[{"value":"18 September 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 April 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 April 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Written consent was obtained from the patient.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written consent was obtained from the patient.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"19"}}