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Autoimmune polyendocrine syndrome type 1
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<h2 id="signs-and-symptoms">Signs and symptoms</h2> <p>APS-1 tends to cause severe symptoms.<a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a> These are present from early in life, usually around 3.5 years of age.<a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a> Common symptoms of APS-1 include: </p> <ul><li><a href="/facts/Chronic_mucocutaneous_candidiasis/16oGkkdH">Chronic mucocutaneous candidiasis</a>.<a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a></li> <li><a href="/facts/Hypoparathyroidism/Dd79cfqo">Hypoparathyroidism</a>.<a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a></li> <li><a href="/facts/Addison%2527s_disease/Lp8AqjEX">Addison's disease</a>.<a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a></li> <li>Ectodermal dystrophy (skin, dental enamel, and nails).</li></ul> <p>APS-1 may also cause: </p> <ul><li><a href="/facts/Autoimmune_hepatitis/aU7dC4Lc">Autoimmune hepatitis</a>.<a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a></li> <li><a href="/facts/Hypogonadism/mqu59lNo">Hypogonadism</a>.<a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a></li> <li><a href="/facts/Vitiligo/d8xPRXQB">Vitiligo</a>.<a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a></li> <li><a href="/facts/Alopecia/uEPKUafl">Alopecia</a>.<a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a></li> <li><a href="/facts/Malabsorption/hWRQd4c5">Malabsorption</a>.</li> <li><a href="/facts/Pernicious_anemia/6WVBYjso">Pernicious anemia</a>.</li> <li><a href="/facts/Cataract/RzN7k7K2">Cataract</a>.</li> <li><a href="/facts/Cerebellar_ataxia/4yUnBW6P">Cerebellar ataxia</a>.<a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a></li></ul> <h2 id="cause">Cause</h2> <p>APS-1 is caused by a mutation in the <a href="/facts/Autoimmune_regulator/jIlSI6sj"><i>AIRE</i> gene</a>, encoding a <a href="/facts/Protein/Jxmagu3E">protein</a> called autoimmune regulator. This is found on the 21q22.3 <a href="/facts/Chromosome/FRGf11FC">chromosome</a> location, hence <a href="/facts/Chromosome_21/F1nQLrCp">chromosome 21</a>.<a class="footnote-ref" id="fnref:14" href="#fn:14"><sup>14</sup></a><a class="footnote-ref" id="fnref:15" href="#fn:15"><sup>15</sup></a><a class="footnote-ref" id="fnref:16" href="#fn:16"><sup>16</sup></a> The <i>AIRE</i> gene may be affected by any of at least 186 <a href="/facts/Mutations/Ee4NnWbY">mutations</a>.<a class="footnote-ref" id="fnref:17" href="#fn:17"><sup>17</sup></a> APS-1 may be inherited in an <a href="/facts/Autosomal_recessive/DsvtPyQU">autosomal recessive</a> manner.<a class="footnote-ref" id="fnref:18" href="#fn:18"><sup>18</sup></a> </p><p>Different mutations are more common in different geographic regions. R139X is a common mutation in <a href="/facts/Sardinia/7GGJNHCx">Sardinia</a>.<a class="footnote-ref" id="fnref:19" href="#fn:19"><sup>19</sup></a> R257* is a common mutation in <a href="/facts/Finland/G5Ak6T91">Finland</a>.<a class="footnote-ref" id="fnref:20" href="#fn:20"><sup>20</sup></a> Both of these mutations are <a href="/facts/Nonsense_mutation/Sqxnqwvv">nonsense mutations</a>: the asterisk and the "X" both indicate a <a href="/facts/Stop_codon/1yuAkq9X">stop codon</a>.<a class="footnote-ref" id="fnref:21" href="#fn:21"><sup>21</sup></a> A 13-base-pair deletion in the <i>AIRE</i> gene, c.967-979del13bp, has been identified in APS-1 patients in <a href="/facts/Norway/wlDRKRTR">Norway</a>, <a href="/facts/British_Isles/4fBquvMU">Britain</a><a class="footnote-ref" id="fnref:22" href="#fn:22"><sup>22</sup></a> and <a href="/facts/North_America/djNjCQIl">North America</a>.<a class="footnote-ref" id="fnref:23" href="#fn:23"><sup>23</sup></a><a class="footnote-ref" id="fnref:24" href="#fn:24"><sup>24</sup></a> </p> <h2 id="pathophysiology">Pathophysiology</h2> <p>APS-1 is due to problems with <a href="/facts/Immune_tolerance/hvDqPHTP">immune tolerance</a>.<a class="footnote-ref" id="fnref:25" href="#fn:25"><sup>25</sup></a> APS-1 causes considerable reactions with both <a href="/facts/IFNW1/lSWI3lvH">interferon omega</a> and <a href="/facts/Interferon_alpha/jQhMAFA3">interferon alpha</a>.<a class="footnote-ref" id="fnref:26" href="#fn:26"><sup>26</sup></a><a class="footnote-ref" id="fnref:27" href="#fn:27"><sup>27</sup></a> There may also be a reaction against <a href="/facts/Interleukin_22/PRd7ePp6">interleukin 22</a>.<a class="footnote-ref" id="fnref:28" href="#fn:28"><sup>28</sup></a> This leads to damage to endocrine organs.<a class="footnote-ref" id="fnref:29" href="#fn:29"><sup>29</sup></a> Common problems include <a href="/facts/Hypercalcaemia/kdEeLaVd">hypercalcaemia</a> and <a href="/facts/Nephrocalcinosis/NnpX3YL1">nephrocalcinosis</a> (due to a lack of <a href="/facts/Calcitonin/E0xGEcr5">calcitonin</a> from the <a href="/facts/Thyroid/bjovTJVu">thyroid</a>), and pituitary problems (such as <a href="/facts/Growth_hormone_deficiency/H2R9x3UU">growth hormone deficiency</a>).<a class="footnote-ref" id="fnref:30" href="#fn:30"><sup>30</sup></a> Antibodies against <a href="/facts/NLRP5/wnQxHmIW">NLRP5</a> may lead to <a href="/facts/Hypoparathyroidism/Dd79cfqo">hypoparathyroidism</a>. </p> <h2 id="diagnosis">Diagnosis</h2> <p>Diagnosis of APS-1 is based on a number of tests, including <a href="/facts/Endoscopy/L4V1fGPN">endoscopy</a>, a <a href="/facts/CT_scan/NusPJ2S8">CT scan</a>,<a class="footnote-ref" id="fnref:31" href="#fn:31"><sup>31</sup></a> a <a href="/facts/Biopsy/A0TdRRlr">biopsy</a> (with histological testing),<a class="footnote-ref" id="fnref:32" href="#fn:32"><sup>32</sup></a> and serum <a href="/facts/Endocrine/PDvN5cpj">endocrine</a> autoantibody screening. </p> <h2 id="treatment">Treatment</h2> <p>Autoimmune polyendocrine syndrome type 1 treatment is based on the symptoms that are presented by the affected individual. Treatments may involve <a href="/facts/Hormone_therapy/8QNWRguk">hormone therapy</a>,<a class="footnote-ref" id="fnref:33" href="#fn:33"><sup>33</sup></a> systemic <a href="/facts/Antifungal/WEk5nS2B">antifungal</a> treatments,<a class="footnote-ref" id="fnref:34" href="#fn:34"><sup>34</sup></a><a class="footnote-ref" id="fnref:35" href="#fn:35"><sup>35</sup></a> and <a href="/facts/Immunosuppression/22GHUHkr">immunosuppression</a>.<a class="footnote-ref" id="fnref:36" href="#fn:36"><sup>36</sup></a> The <a href="/facts/JAK-STAT_signaling_pathway/t31RBT3X">JAK-STAT</a> inhibitor <a href="/facts/Ruxolitinib/WUkFQnnW">ruxolitinib</a> is being investigated as a treatment specifically for its normalizing effect on <a href="/facts/Interferon-gamma/r51CXVph">interferon-gamma</a>.<a class="footnote-ref" id="fnref:37" href="#fn:37"><sup>37</sup></a> </p> <h2 id="history">History</h2> <p>APS-1 may also be known as autoimmunity endocrinopathy candidiasis ectodermal dystrophy / dysplasia (APECED), autoimmune polyglandular syndrome type 1, Whitaker syndrome,<a class="footnote-ref" id="fnref:38" href="#fn:38"><sup>38</sup></a> or candidiasis-hypoparathyroidism-Addison's disease syndrome.<a class="footnote-ref" id="fnref:39" href="#fn:39"><sup>39</sup></a> </p> <h2 id="see-also">See also</h2> <ul><li><a href="/facts/Autoimmune_polyendocrine_syndrome_type_2/VEejjQa7">Autoimmune polyendocrine syndrome type 2</a></li> <li><a href="/facts/IPEX_syndrome/AMdKHGb4">IPEX syndrome</a></li> <li><a href="/facts/Autoimmune_polyendocrine_syndrome/hNmcov4p">Autoimmune polyendocrine syndrome</a></li></ul> <h2 id="further-reading">Further reading</h2> <ul><li>De Martino L, Capalbo D, Improda N, Lorello P, Ungaro C, Di Mase R, et al. (1 January 2016). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4992815">"Novel Findings into AIRE Genetics and Functioning: Clinical Implications"</a>. <i>Frontiers in Pediatrics</i>. 4: 86. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.3389%2Ffped.2016.00086">10.3389/fped.2016.00086</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4992815">4992815</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/27597936">27597936</a>.</li> <li>Peterson P, Pitkänen J, Sillanpää N, Krohn K (March 2004). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1808970">"Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED): a model disease to study molecular aspects of endocrine autoimmunity"</a>. <i>Clinical and Experimental Immunology</i>. 135 (3): 348–57. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1111%2Fj.1365-2249.2004.02384.x">10.1111/j.1365-2249.2004.02384.x</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1808970">1808970</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/15008965">15008965</a>.</li> <li>Capalbo D, De Martino L, Giardino G, Di Mase R, Di Donato I, Parenti G, et al. (2012). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485503">"Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy: insights into genotype-phenotype correlation"</a>. <i>International Journal of Endocrinology</i>. 2012: 353250. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1155%2F2012%2F353250">10.1155/2012/353250</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485503">3485503</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/23133448">23133448</a>.</li></ul> <h2 id="external-links">External links</h2> <ul><li><a href="https://www.ncbi.nlm.nih.gov/pubmed">PubMed</a></li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>"AIRE gene". Genetics Home Reference. Archived from the original on 2017-04-05. Retrieved 2017-04-04. <a href="https://ghr.nlm.nih.gov/gene/AIRE#location" target="_blank">https://ghr.nlm.nih.gov/gene/AIRE#location</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>"APECED". Archived from the original on 2017-04-06. Retrieved 2017-04-04. <a href="https://ghr.nlm.nih.gov/condition/autoimmune-polyendocrinopathy-candidiasis-ectodermal-dystrophy#inheritance" target="_blank">https://ghr.nlm.nih.gov/condition/autoimmune-polyendocrinopathy-candidiasis-ectodermal-dystrophy#inheritance</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Shoenfeld Y, Cervera R, Gershwin ME (2010-06-08). Diagnostic Criteria in Autoimmune Diseases. Springer Science & Business Media. p. 265. ISBN 9781603272858. Archived from the original on 2023-01-14. Retrieved 2020-11-05. <a href="9781603272858" target="_blank">9781603272858</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>Meloni, Antonella; Willcox, Nick; Meager, Anthony; Atzeni, Michela; Wolff, Anette S. B.; Husebye, Eystein S.; Furcas, Maria; Rosatelli, Maria Cristina; Cao, Antonio; Congia, Mauro (April 2012). "Autoimmune Polyendocrine Syndrome Type 1: An Extensive Longitudinal Study in Sardinian Patients". The Journal of Clinical Endocrinology & Metabolism. 97 (4): 1114–1124. doi:10.1210/jc.2011-2461. ISSN 0021-972X. PMID 22344197. <a href="https://doi.org/10.1210%2Fjc.2011-2461" target="_blank">https://doi.org/10.1210%2Fjc.2011-2461</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Meloni, Antonella; Willcox, Nick; Meager, Anthony; Atzeni, Michela; Wolff, Anette S. B.; Husebye, Eystein S.; Furcas, Maria; Rosatelli, Maria Cristina; Cao, Antonio; Congia, Mauro (April 2012). "Autoimmune Polyendocrine Syndrome Type 1: An Extensive Longitudinal Study in Sardinian Patients". The Journal of Clinical Endocrinology & Metabolism. 97 (4): 1114–1124. doi:10.1210/jc.2011-2461. ISSN 0021-972X. PMID 22344197. <a href="https://doi.org/10.1210%2Fjc.2011-2461" target="_blank">https://doi.org/10.1210%2Fjc.2011-2461</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>Meloni, Antonella; Willcox, Nick; Meager, Anthony; Atzeni, Michela; Wolff, Anette S. B.; Husebye, Eystein S.; Furcas, Maria; Rosatelli, Maria Cristina; Cao, Antonio; Congia, Mauro (April 2012). "Autoimmune Polyendocrine Syndrome Type 1: An Extensive Longitudinal Study in Sardinian Patients". The Journal of Clinical Endocrinology & Metabolism. 97 (4): 1114–1124. doi:10.1210/jc.2011-2461. ISSN 0021-972X. PMID 22344197. <a href="https://doi.org/10.1210%2Fjc.2011-2461" target="_blank">https://doi.org/10.1210%2Fjc.2011-2461</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>Meloni, Antonella; Willcox, Nick; Meager, Anthony; Atzeni, Michela; Wolff, Anette S. B.; Husebye, Eystein S.; Furcas, Maria; Rosatelli, Maria Cristina; Cao, Antonio; Congia, Mauro (April 2012). "Autoimmune Polyendocrine Syndrome Type 1: An Extensive Longitudinal Study in Sardinian Patients". The Journal of Clinical Endocrinology & Metabolism. 97 (4): 1114–1124. doi:10.1210/jc.2011-2461. ISSN 0021-972X. PMID 22344197. <a href="https://doi.org/10.1210%2Fjc.2011-2461" target="_blank">https://doi.org/10.1210%2Fjc.2011-2461</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>Meloni, Antonella; Willcox, Nick; Meager, Anthony; Atzeni, Michela; Wolff, Anette S. B.; Husebye, Eystein S.; Furcas, Maria; Rosatelli, Maria Cristina; Cao, Antonio; Congia, Mauro (April 2012). "Autoimmune Polyendocrine Syndrome Type 1: An Extensive Longitudinal Study in Sardinian Patients". The Journal of Clinical Endocrinology & Metabolism. 97 (4): 1114–1124. doi:10.1210/jc.2011-2461. ISSN 0021-972X. PMID 22344197. <a href="https://doi.org/10.1210%2Fjc.2011-2461" target="_blank">https://doi.org/10.1210%2Fjc.2011-2461</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>Meloni, Antonella; Willcox, Nick; Meager, Anthony; Atzeni, Michela; Wolff, Anette S. B.; Husebye, Eystein S.; Furcas, Maria; Rosatelli, Maria Cristina; Cao, Antonio; Congia, Mauro (April 2012). "Autoimmune Polyendocrine Syndrome Type 1: An Extensive Longitudinal Study in Sardinian Patients". The Journal of Clinical Endocrinology & Metabolism. 97 (4): 1114–1124. doi:10.1210/jc.2011-2461. ISSN 0021-972X. PMID 22344197. <a href="https://doi.org/10.1210%2Fjc.2011-2461" target="_blank">https://doi.org/10.1210%2Fjc.2011-2461</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>Meloni, Antonella; Willcox, Nick; Meager, Anthony; Atzeni, Michela; Wolff, Anette S. B.; Husebye, Eystein S.; Furcas, Maria; Rosatelli, Maria Cristina; Cao, Antonio; Congia, Mauro (April 2012). "Autoimmune Polyendocrine Syndrome Type 1: An Extensive Longitudinal Study in Sardinian Patients". The Journal of Clinical Endocrinology & Metabolism. 97 (4): 1114–1124. doi:10.1210/jc.2011-2461. ISSN 0021-972X. PMID 22344197. <a href="https://doi.org/10.1210%2Fjc.2011-2461" target="_blank">https://doi.org/10.1210%2Fjc.2011-2461</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> <li id="fn:11"><p>Meloni, Antonella; Willcox, Nick; Meager, Anthony; Atzeni, Michela; Wolff, Anette S. B.; Husebye, Eystein S.; Furcas, Maria; Rosatelli, Maria Cristina; Cao, Antonio; Congia, Mauro (April 2012). "Autoimmune Polyendocrine Syndrome Type 1: An Extensive Longitudinal Study in Sardinian Patients". The Journal of Clinical Endocrinology & Metabolism. 97 (4): 1114–1124. doi:10.1210/jc.2011-2461. ISSN 0021-972X. PMID 22344197. <a href="https://doi.org/10.1210%2Fjc.2011-2461" target="_blank">https://doi.org/10.1210%2Fjc.2011-2461</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></p></li> <li id="fn:12"><p>Meloni, Antonella; Willcox, Nick; Meager, Anthony; Atzeni, Michela; Wolff, Anette S. B.; Husebye, Eystein S.; Furcas, Maria; Rosatelli, Maria Cristina; Cao, Antonio; Congia, Mauro (April 2012). "Autoimmune Polyendocrine Syndrome Type 1: An Extensive Longitudinal Study in Sardinian Patients". The Journal of Clinical Endocrinology & Metabolism. 97 (4): 1114–1124. doi:10.1210/jc.2011-2461. ISSN 0021-972X. PMID 22344197. <a href="https://doi.org/10.1210%2Fjc.2011-2461" target="_blank">https://doi.org/10.1210%2Fjc.2011-2461</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></p></li> <li id="fn:13"><p>Orlova, Elizaveta M; Sozaeva, Leila S; Kareva, Maria A; Oftedal, Bergithe E; Wolff, Anette S B; Breivik, Lars; Zakharova, Ekaterina Y; Ivanova, Olga N; Kämpe, Olle; Dedov, Ivan I; Knappskog, Per M (2017-07-20). "Expanding the Phenotypic and Genotypic Landscape of Autoimmune Polyendocrine Syndrome Type 1". The Journal of Clinical Endocrinology & Metabolism. 102 (9): 3546–3556. doi:10.1210/jc.2017-00139. ISSN 0021-972X. PMID 28911151. S2CID 3822560. <a href="https://doi.org/10.1210%2Fjc.2017-00139" target="_blank">https://doi.org/10.1210%2Fjc.2017-00139</a> <a href="#fnref:13" class="footnote-back-ref">↩</a></p></li> <li id="fn:14"><p>"AIRE gene". Genetics Home Reference. Archived from the original on 2017-04-05. Retrieved 2017-04-04. <a href="https://ghr.nlm.nih.gov/gene/AIRE#location" target="_blank">https://ghr.nlm.nih.gov/gene/AIRE#location</a> <a href="#fnref:14" class="footnote-back-ref">↩</a></p></li> <li id="fn:15"><p>"APECED". Archived from the original on 2017-04-06. Retrieved 2017-04-04. <a href="https://ghr.nlm.nih.gov/condition/autoimmune-polyendocrinopathy-candidiasis-ectodermal-dystrophy#inheritance" target="_blank">https://ghr.nlm.nih.gov/condition/autoimmune-polyendocrinopathy-candidiasis-ectodermal-dystrophy#inheritance</a> <a href="#fnref:15" class="footnote-back-ref">↩</a></p></li> <li id="fn:16"><p>"Autoimmune Polyglandular Syndrome Type 1 (APS-1)". NIH: National Institute of Allergy and Infectious Diseases. Archived from the original on 2017-04-17. Retrieved 2017-04-16. <a href="https://www.niaid.nih.gov/diseases-conditions/autoimmune-polyglandular-syndrome-type-1-aps-1" target="_blank">https://www.niaid.nih.gov/diseases-conditions/autoimmune-polyglandular-syndrome-type-1-aps-1</a> <a href="#fnref:16" class="footnote-back-ref">↩</a></p></li> <li id="fn:17"><p>D.N. Cooper; E.V. Ball; P.D. Stenson; A.D. Phillips; K. Evans; S. Heywood; M.J. Hayden; M.M. Chapman; M.E Mort; L. Azevedo; D.S. Millar (eds.). "AIRE". The Human Gene Mutation Database. Institute of Medical Genetics in Cardiff. Archived from the original on 22 August 2023. Retrieved 22 August 2023. <a href="https://www.hgmd.cf.ac.uk/ac/gene.php?gene=AIRE" target="_blank">https://www.hgmd.cf.ac.uk/ac/gene.php?gene=AIRE</a> <a href="#fnref:17" class="footnote-back-ref">↩</a></p></li> <li id="fn:18"><p>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 (1998). 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