{{Short description|Autoimmune condition causing dysfunction of endocrine glands}} {{Infobox medical condition (new) | name = Autoimmune polyendocrine syndrome type 1 | image = File:Autosomal recessive - en.svg | caption = Autoimmune polyendocrine syndrome type 1 is autosomal recessive | diseasesDB_mult = | synonyms = '''Autoimmune polyendocrinopathy-candidiasis–ectodermal dystrophy/dysplasia''' ('''APECED'''), '''Autoimmune polyglandular syndrome type 1''', '''Whitaker syndrome''', '''Candidiasis-hypoparathyroidism–Addison's disease syndrome''' | symptoms = chronic mucocutaneous candidiasis | onset = | duration = | types = | causes = mutation in AIRE gene | risks = | diagnosis = CT scan, biopsy | differential = | prevention = | treatment = hormone therapy, antifungals, immunosuppression | medication = | prognosis = | frequency = | deaths = | specialty = endocrinology, medical genetics }} '''Autoimmune polyendocrine syndrome type 1''' ('''APS-1'''), is a subtype of autoimmune polyendocrine syndrome (autoimmune polyglandular syndrome). It causes the dysfunction of multiple endocrine glands due to autoimmunity. It is a genetic disorder, inherited in autosomal recessive fashion due to a defect in the ''AIRE'' gene (autoimmune regulator), which is located on chromosome 21 and normally confers immune tolerance.<ref name="nih">{{Cite web |title=AIRE gene |url=https://medlineplus.gov/genetics/gene/aire/ |url-status=live |archive-url=https://web.archive.org/web/20170405170953/https://ghr.nlm.nih.gov/gene/AIRE#location |archive-date=2017-04-05 |access-date=2017-04-04 |website=Genetics Home Reference}}</ref><ref name="nih2">{{Cite web |title=APECED |url=https://medlineplus.gov/genetics/condition/autoimmune-polyendocrinopathy-candidiasis-ectodermal-dystrophy/ |url-status=live |archive-url=https://web.archive.org/web/20170406020540/https://ghr.nlm.nih.gov/condition/autoimmune-polyendocrinopathy-candidiasis-ectodermal-dystrophy#inheritance |archive-date=2017-04-06 |access-date=2017-04-04}}</ref><ref>{{Cite book |last=Shoenfeld |first=Yehuda |url=https://books.google.com/books?id=A_vtzMxtd9AC&q=autoimmune+polyendocrine+syndromeS&pg=PA265 |title=Diagnostic Criteria in Autoimmune Diseases |last2=Cervera |first2=Ricard |last3=Gershwin |first3=M. Eric |date=2010-06-08 |publisher=Springer Science & Business Media |isbn=978-1-60327-285-8 |page=265 |access-date=2020-11-05 |archive-url=https://web.archive.org/web/20230114133447/https://books.google.com/books?id=A_vtzMxtd9AC&q=autoimmune+polyendocrine+syndromes&pg=PA265 |archive-date=2023-01-14 |url-status=live |name-list-style=vanc}}</ref>
== Signs and symptoms == APS-1 tends to cause severe symptoms.<ref name=":1">{{Cite journal |last=Meloni |first=Antonella |last2=Willcox |first2=Nick |last3=Meager |first3=Anthony |last4=Atzeni |first4=Michela |last5=Wolff |first5=Anette S. B. |last6=Husebye |first6=Eystein S. |last7=Furcas |first7=Maria |last8=Rosatelli |first8=Maria Cristina |last9=Cao |first9=Antonio |last10=Congia |first10=Mauro |date=April 2012 |title=Autoimmune Polyendocrine Syndrome Type 1: An Extensive Longitudinal Study in Sardinian Patients |journal=The Journal of Clinical Endocrinology & Metabolism |volume=97 |issue=4 |pages=1114–1124 |doi=10.1210/jc.2011-2461 |issn=0021-972X |pmid=22344197 |doi-access=free}}</ref> These are present from early in life, usually around 3.5 years of age.<ref name=":1" /> Common symptoms of APS-1 include: * Chronic mucocutaneous candidiasis.<ref name=":1" /> * Hypoparathyroidism.<ref name=":1" /> * Addison's disease.<ref name=":1" /> * Ectodermal dystrophy (skin, dental enamel, and nails).
APS-1 may also cause: * Autoimmune hepatitis.<ref name=":1" /> * Hypogonadism.<ref name=":1" /> * Vitiligo.<ref name=":1" /> * Alopecia.<ref name=":1" /> * Malabsorption. * Pernicious anemia. * Cataract. * Cerebellar ataxia.<ref name=":2">{{Cite journal |last=Orlova |first=Elizaveta M |last2=Sozaeva |first2=Leila S |last3=Kareva |first3=Maria A |last4=Oftedal |first4=Bergithe E |last5=Wolff |first5=Anette S B |last6=Breivik |first6=Lars |last7=Zakharova |first7=Ekaterina Y |last8=Ivanova |first8=Olga N |last9=Kämpe |first9=Olle |last10=Dedov |first10=Ivan I |last11=Knappskog |first11=Per M |date=2017-07-20 |title=Expanding the Phenotypic and Genotypic Landscape of Autoimmune Polyendocrine Syndrome Type 1 |journal=The Journal of Clinical Endocrinology & Metabolism |volume=102 |issue=9 |pages=3546–3556 |doi=10.1210/jc.2017-00139 |issn=0021-972X |pmid=28911151 |s2cid=3822560 |doi-access=free}}</ref>
== Cause == 66x66px|left|thumb|Chromosome 21 APS-1 is caused by a mutation in the ''AIRE'' gene, encoding a protein called autoimmune regulator. This is found on the 21q22.3 chromosome location, hence chromosome 21.<ref name="nih" /><ref name="nih2" /><ref>{{Cite web |title=Autoimmune Polyglandular Syndrome Type 1 (APS-1) |url=https://www.niaid.nih.gov/diseases-conditions/autoimmune-polyglandular-syndrome-type-1-aps-1 |archive-url=https://web.archive.org/web/20170417072131/https://www.niaid.nih.gov/diseases-conditions/autoimmune-polyglandular-syndrome-type-1-aps-1 |archive-date=2017-04-17 |access-date=2017-04-16 |website=NIH: National Institute of Allergy and Infectious Diseases}}</ref> The ''AIRE'' gene may be affected by any of at least 186 mutations.<ref name="hgmd">{{Cite web |editor2-last=E.V. Ball |editor3-last=P.D. Stenson |editor4-last=A.D. Phillips |editor5-last=K. Evans |editor6-last=S. Heywood |editor7-last=M.J. Hayden |editor8-last=M.M. Chapman |editor9-last=M.E Mort |title=AIRE |url=https://www.hgmd.cf.ac.uk/ac/gene.php?gene=AIRE |url-access=registration |url-status=live |archive-url=https://web.archive.org/web/20230822193334/https://www.hgmd.cf.ac.uk/ac/gene.php?gene=AIRE |archive-date=22 August 2023 |access-date=22 August 2023 |website=The Human Gene Mutation Database |publisher=Institute of Medical Genetics in Cardiff |editor1=D.N. Cooper |editor10=L. Azevedo |editor11=D.S. Millar}}</ref> APS-1 may be inherited in an autosomal recessive manner.<ref name="pmid9837820">{{Cite journal |vauthors=Pearce SH, Cheetham T, Imrie H, Vaidya B, Barnes ND, Bilous RW, Carr D, Meeran K, Shaw NJ, Smith CS, Toft AD, Williams G, Kendall-Taylor P |year=1998 |title=A Common and Recurrent 13-bp Deletion in the Autoimmune Regulator Gene in British Kindreds with Autoimmune Polyendocrinopathy Type 1 |journal=American Journal of Human Genetics |volume=63 |issue=6 |pages=1675–1684 |doi=10.1086/302145 |pmc=1377639 |pmid=9837820 |doi-access=free}}</ref>
Different mutations are more common in different geographic regions. R139X is a common mutation in Sardinia.<ref name=":1" /> R257* is a common mutation in Finland.<ref name=":2" /> Both of these mutations are nonsense mutations: the asterisk and the "X" both indicate a stop codon.<ref name=hgmd/> A 13-base-pair deletion in the ''AIRE'' gene, c.967-979del13bp, has been identified in APS-1 patients in Norway, Britain<ref name=pmid9837820/> and North America.<ref>{{Cite journal |vauthors=Bruserud Ø, Oftedal BE, Wolff AB, Husebye ES |year=2016 |title=''AIRE''-mutations and autoimmune disease |journal=Current Opinion in Immunology |volume=43 |pages=8–15 |doi=10.1016/j.coi.2016.07.003 |pmid=27504588}}</ref><ref>{{Cite journal |vauthors=Qian G, Yan X, Xuan J, Zheng D, He Z, Shen J |year=2022 |title=A novel AIRE mutation leads to autoimmune polyendocrine syndrome type-1 |journal=Frontiers in Cell and Developmental Biology |volume=10 |doi=10.3389/fcell.2022.948350 |pmc=9441485 |pmid=36072346 |id=948350 |doi-access=free}}</ref>
== Pathophysiology == APS-1 is due to problems with immune tolerance.<ref>{{Cite journal |display-authors=6 |vauthors=De Martino L, Capalbo D, Improda N, D'Elia F, Di Mase R, D'Assante R, D'Acunzo I, Pignata C, Salerno M |date=October 2013 |title=APECED: A Paradigm of Complex Interactions between Genetic Background and Susceptibility Factors |journal=Frontiers in Immunology |volume=4 |page=331 |doi=10.3389/fimmu.2013.00331 |pmc=3805967 |pmid=24167503 |doi-access=free}}</ref> APS-1 causes considerable reactions with both interferon omega and interferon alpha.<ref name=":1" /><ref name=":0">{{Cite web |last=Aldasouqi |first=Saleh A. |date=15 November 2016 |title=Type I Polyglandular Autoimmune Syndrome |url=http://emedicine.medscape.com/article/124183-overview |url-status=live |archive-url=https://web.archive.org/web/20081209071028/http://emedicine.medscape.com:80/article/124183-overview |archive-date=2008-12-09 |access-date=20 November 2020 |website=emedicine.medscape.com |publisher=Medscape}}</ref> There may also be a reaction against interleukin 22.<ref name=":1" /> This leads to damage to endocrine organs.<ref name=":1" /> Common problems include hypercalcaemia and nephrocalcinosis (due to a lack of calcitonin from the thyroid), and pituitary problems (such as growth hormone deficiency).<ref name=":1" /> Antibodies against NLRP5 may lead to hypoparathyroidism.{{citation needed|date=November 2021}}
== Diagnosis == thumb|Endoscope Diagnosis of APS-1 is based on a number of tests, including endoscopy, a CT scan,<ref name=":0" /> a biopsy (with histological testing),<ref name=":0" /> and serum endocrine autoantibody screening.
== Treatment == Autoimmune polyendocrine syndrome type 1 treatment is based on the symptoms that are presented by the affected individual. Treatments may involve hormone therapy,<ref name="pha" /> systemic antifungal treatments,<ref name=":1" /><ref name="pha" /> and immunosuppression.<ref name="pha">{{Cite web |last=INSERM RESERVED |title=Orphanet: Autoimmune polyendocrinopathy type 1 |url=http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=3453 |url-status=live |archive-url=https://web.archive.org/web/20170423064451/http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=3453 |archive-date=2017-04-23 |access-date=2017-04-22 |website=www.orpha.net |language=en}}</ref> The JAK-STAT inhibitor ruxolitinib is being investigated as a treatment specifically for its normalizing effect on interferon-gamma.<ref>{{Cite journal |last=Oikonomou |first=Vasileios |last2=Smith |first2=Grace |last3=Constantine |first3=Gregory M. |last4=Schmitt |first4=Monica M. |last5=Ferré |first5=Elise M.N. |last6=Alejo |first6=Julie C. |last7=Riley |first7=Deanna |last8=Kumar |first8=Dhaneshwar |last9=Dos Santos Dias |first9=Lucas |last10=Pechacek |first10=Joseph |last11=Hadjiyannis |first11=Yannis |last12=Webb |first12=Taura |last13=Seifert |first13=Bryce A. |last14=Ghosh |first14=Rajarshi |last15=Walkiewicz |first15=Magdalena |date=2024-05-30 |title=The Role of Interferon-γ in Autoimmune Polyendocrine Syndrome Type 1 |journal=New England Journal of Medicine |language=en |volume=390 |issue=20 |pages=1873–1884 |doi=10.1056/NEJMoa2312665 |issn=0028-4793 |pmc=11323209 |pmid=38810185}}</ref>
== History == APS-1 may also be known as autoimmunity endocrinopathy candidiasis ectodermal dystrophy / dysplasia (APECED),{{Citation needed|date=October 2021}} autoimmune polyglandular syndrome type 1,{{Citation needed|date=October 2021}} Whitaker syndrome,<ref name=":0" /> or candidiasis-hypoparathyroidism-Addison's disease syndrome.<ref name="greenspan">{{Cite book |last=Greenspan |first=F. S. |url=https://archive.org/details/isbn_9780071402972/page/103 |title=Basic clinical endocrinology |last2=Gardner |first2=D. C. |publisher=McGraw-Hill |year=2004 |isbn=978-0-07-140297-2 |location=New York |pages=[https://archive.org/details/isbn_9780071402972/page/103 103] |language=en |url-access=registration}}</ref>
== See also == * Autoimmune polyendocrine syndrome type 2 * IPEX syndrome * Autoimmune polyendocrine syndrome
== References == {{Reflist|32em}}
== Further reading == {{refbegin}} * {{Cite journal |display-authors=6 |vauthors=De Martino L, Capalbo D, Improda N, Lorello P, Ungaro C, Di Mase R, Cirillo E, Pignata C, Salerno M |date=1 January 2016 |title=Novel Findings into AIRE Genetics and Functioning: Clinical Implications |journal=Frontiers in Pediatrics |volume=4 |page=86 |doi=10.3389/fped.2016.00086 |pmc=4992815 |pmid=27597936 |doi-access=free}} * {{Cite journal |vauthors=Peterson P, Pitkänen J, Sillanpää N, Krohn K |date=March 2004 |title=Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED): a model disease to study molecular aspects of endocrine autoimmunity |journal=Clinical and Experimental Immunology |volume=135 |issue=3 |pages=348–57 |doi=10.1111/j.1365-2249.2004.02384.x |pmc=1808970 |pmid=15008965}} * {{Cite journal |display-authors=6 |vauthors=Capalbo D, De Martino L, Giardino G, Di Mase R, Di Donato I, Parenti G, Vajro P, Pignata C, Salerno M |year=2012 |title=Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy: insights into genotype-phenotype correlation |journal=International Journal of Endocrinology |volume=2012 |article-number=353250 |doi=10.1155/2012/353250 |pmc=3485503 |pmid=23133448 |doi-access=free}} {{refend}}
== External links == * [https://www.ncbi.nlm.nih.gov/pubmed PubMed] {{Medical resources | DiseasesDB = 29212 | ICD10 = {{ICD10|E|31|0|e|20}} | ICD9 = {{ICD9|258.1}} | ICDO = | OMIM = 240300 | MedlinePlus = | eMedicineSubj = med | eMedicineTopic = 1867 | MeshID = D016884 | Orphanet = 3453 }}{{Scholia|topic}} {{Disorders involving multiple endocrine glands}} {{Hypersensitivity and autoimmune diseases}} {{Transcription factor deficiencies}}
Category:Endocrine diseases Category:Autoimmune diseases Category:Transcription factor deficiencies Category:Syndromes Category:Finnish heritage disease