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Autoimmune polyendocrine syndrome type 1

From Wikipedia, the free encyclopedia
Autoimmune polyendocrine syndrome type 1
Other namesAutoimmune polyendocrinopathy-candidiasis–ectodermal dystrophy/dysplasia (APECED),

Autoimmune polyglandular syndrome type 1, Whitaker syndrome,

Candidiasis-hypoparathyroidism–Addison"s disease syndrome
Autoimmune polyendocrine syndrome type 1 is autosomal recessive
SpecialtyEndocrinology, medical genetics
Symptomschronic mucocutaneous candidiasis
Causesmutation in AIRE gene
Diagnostic methodCT scan, biopsy
Treatmenthormone therapy, antifungals, immunosuppression

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.[1][2][3]

Signs and symptoms

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APS-1 tends to cause severe symptoms.[4] These are present from early in life, usually around 3.5 years of age.[4] Common symptoms of APS-1 include:

APS-1 may also cause:

Cause

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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.[1][2][6] The AIRE gene may be affected by any of at least 186 mutations.[7] APS-1 may be inherited in an autosomal recessive manner.[8]

Different mutations are more common in different geographic regions. R139X is a common mutation in Sardinia.[4] R257* is a common mutation in Finland.[5] Both of these mutations are nonsense mutations: the asterisk and the "X" both indicate a stop codon.[7] A 13-base-pair deletion in the AIRE gene, c.967-979del13bp, has been identified in APS-1 patients in Norway, Britain[8] and North America.[9][10]

Pathophysiology

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APS-1 is due to problems with immune tolerance.[11] APS-1 causes considerable reactions with both interferon omega and interferon alpha.[4][12] There may also be a reaction against interleukin 22.[4] This leads to damage to endocrine organs.[4] Common problems include hypercalcaemia and nephrocalcinosis (due to a lack of calcitonin from the thyroid), and pituitary problems (such as growth hormone deficiency).[4] Antibodies against NLRP5 may lead to hypoparathyroidism.[citation needed]

Diagnosis

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Endoscope

Diagnosis of APS-1 is based on a number of tests, including endoscopy, a CT scan,[12] a biopsy (with histological testing),[12] and serum endocrine autoantibody screening.

Treatment

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Autoimmune polyendocrine syndrome type 1 treatment is based on the symptoms that are presented by the affected individual. Treatments may involve hormone therapy,[13] systemic antifungal treatments,[4][13] and immunosuppression.[13] The JAK-STAT inhibitor ruxolitinib is being investigated as a treatment specifically for its normalizing effect on interferon-gamma.[14]

History

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APS-1 may also be known as autoimmunity endocrinopathy candidiasis ectodermal dystrophy / dysplasia (APECED),[citation needed] autoimmune polyglandular syndrome type 1,[citation needed] Whitaker syndrome,[12] or candidiasis-hypoparathyroidism-Addison"s disease syndrome.[15]

See also

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References

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  1. ^ a b "AIRE gene". Genetics Home Reference. Archived from the original on 2017-04-05. Retrieved 2017-04-04.
  2. ^ a b "APECED". Archived from the original on 2017-04-06. Retrieved 2017-04-04.
  3. ^ 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.
  4. ^ a b c d e f g h i j k l m n o 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 22344197.1114-1124&rft.date=2012-04&rft.issn=0021-972X&rft_id=info:pmid/22344197&rft_id=info:doi/10.1210/jc.2011-2461&rft.aulast=Meloni&rft.aufirst=Antonella&rft.au=Willcox,+Nick&rft.au=Meager,+Anthony&rft.au=Atzeni,+Michela&rft.au=Wolff,+Anette+S.+B.&rft.au=Husebye,+Eystein+S.&rft.au=Furcas,+Maria&rft.au=Rosatelli,+Maria+Cristina&rft.au=Cao,+Antonio&rft.au=Congia,+Mauro&rft_id=https://doi.org/10.1210%2Fjc.2011-2461&rfr_id=info:sid/en.wikipedia.org:Autoimmune+polyendocrine+syndrome+type+1" class="Z3988">
  5. ^ a b 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 3822560.3546-3556&rft.date=2017-07-20&rft.issn=0021-972X&rft_id=https://api.semanticscholar.org/CorpusID:3822560#id-name=S2CID&rft_id=info:pmid/28911151&rft_id=info:doi/10.1210/jc.2017-00139&rft.aulast=Orlova&rft.aufirst=Elizaveta+M&rft.au=Sozaeva,+Leila+S&rft.au=Kareva,+Maria+A&rft.au=Oftedal,+Bergithe+E&rft.au=Wolff,+Anette+S+B&rft.au=Breivik,+Lars&rft.au=Zakharova,+Ekaterina+Y&rft.au=Ivanova,+Olga+N&rft.au=Kämpe,+Olle&rft.au=Dedov,+Ivan+I&rft.au=Knappskog,+Per+M&rft_id=https://doi.org/10.1210%2Fjc.2017-00139&rfr_id=info:sid/en.wikipedia.org:Autoimmune+polyendocrine+syndrome+type+1" class="Z3988">
  6. ^ "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.
  7. ^ a b 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.
  8. ^ a b 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). "A Common and Recurrent 13-bp Deletion in the Autoimmune Regulator Gene in British Kindreds with Autoimmune Polyendocrinopathy Type 1". American Journal of Human Genetics. 63 (6): 1675–1684. doi:10.1086/302145. PMC 1377639. PMID 9837820.1675-1684&rft.date=1998&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1377639#id-name=PMC&rft_id=info:pmid/9837820&rft_id=info:doi/10.1086/302145&rft.aulast=Pearce&rft.aufirst=SH&rft.au=Cheetham,+T&rft.au=Imrie,+H&rft.au=Vaidya,+B&rft.au=Barnes,+ND&rft.au=Bilous,+RW&rft.au=Carr,+D&rft.au=Meeran,+K&rft.au=Shaw,+NJ&rft.au=Smith,+CS&rft.au=Toft,+AD&rft.au=Williams,+G&rft.au=Kendall-Taylor,+P&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1377639&rfr_id=info:sid/en.wikipedia.org:Autoimmune+polyendocrine+syndrome+type+1" class="Z3988">
  9. ^ Bruserud Ø, Oftedal BE, Wolff AB, Husebye ES (2016). "AIRE-mutations and autoimmune disease". Current Opinion in Immunology. 43: 8–15. doi:10.1016/j.coi.2016.07.003. PMID 27504588.8-15&rft.date=2016&rft_id=info:doi/10.1016/j.coi.2016.07.003&rft_id=info:pmid/27504588&rft.aulast=Bruserud&rft.aufirst=Ø&rft.au=Oftedal,+BE&rft.au=Wolff,+AB&rft.au=Husebye,+ES&rfr_id=info:sid/en.wikipedia.org:Autoimmune+polyendocrine+syndrome+type+1" class="Z3988">
  10. ^ Qian G, Yan X, Xuan J, Zheng D, He Z, Shen J (2022). "A novel AIRE mutation leads to autoimmune polyendocrine syndrome type-1". Frontiers in Cell and Developmental Biology. 10. doi:10.3389/fcell.2022.948350. PMC 9441485. PMID 36072346. 948350.
  11. ^ De Martino L, Capalbo D, Improda N, D"Elia F, Di Mase R, D"Assante R, et al. (October 2013). "APECED: A Paradigm of Complex Interactions between Genetic Background and Susceptibility Factors". Frontiers in Immunology. 4: 331. doi:10.3389/fimmu.2013.00331. PMC 3805967. PMID 24167503.
  12. ^ a b c d Aldasouqi, Saleh A. (15 November 2016). "Type I Polyglandular Autoimmune Syndrome". emedicine.medscape.com. Medscape. Archived from the original on 2008-12-09. Retrieved 20 November 2020.
  13. ^ a b c INSERM RESERVED. "Orphanet: Autoimmune polyendocrinopathy type 1". www.orpha.net. Archived from the original on 2017-04-23. Retrieved 2017-04-22.
  14. ^ Oikonomou, Vasileios; Smith, Grace; Constantine, Gregory M.; Schmitt, Monica M.; Ferré, Elise M.N.; Alejo, Julie C.; Riley, Deanna; Kumar, Dhaneshwar; Dos Santos Dias, Lucas; Pechacek, Joseph; Hadjiyannis, Yannis; Webb, Taura; Seifert, Bryce A.; Ghosh, Rajarshi; Walkiewicz, Magdalena (2024-05-30). "The Role of Interferon-γ in Autoimmune Polyendocrine Syndrome Type 1". New England Journal of Medicine. 390 (20): 1873–1884. doi:10.1056/NEJMoa2312665. ISSN 0028-4793. PMC 11323209. PMID 38810185.1873-1884&rft.date=2024-05-30&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11323209#id-name=PMC&rft.issn=0028-4793&rft_id=info:pmid/38810185&rft_id=info:doi/10.1056/NEJMoa2312665&rft.aulast=Oikonomou&rft.aufirst=Vasileios&rft.au=Smith,+Grace&rft.au=Constantine,+Gregory+M.&rft.au=Schmitt,+Monica+M.&rft.au=Ferré,+Elise+M.N.&rft.au=Alejo,+Julie+C.&rft.au=Riley,+Deanna&rft.au=Kumar,+Dhaneshwar&rft.au=Dos+Santos+Dias,+Lucas&rft.au=Pechacek,+Joseph&rft.au=Hadjiyannis,+Yannis&rft.au=Webb,+Taura&rft.au=Seifert,+Bryce+A.&rft.au=Ghosh,+Rajarshi&rft.au=Walkiewicz,+Magdalena&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11323209&rfr_id=info:sid/en.wikipedia.org:Autoimmune+polyendocrine+syndrome+type+1" class="Z3988">
  15. ^ Greenspan, F. S.; Gardner, D. C. (2004). Basic clinical endocrinology. New York: McGraw-Hill. pp. 103. ISBN 978-0-07-140297-2.

Further reading

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