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Autoimmune polyendocrine syndrome type 1
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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.cite-ref-nih-1-0[1]cite-ref-nih2-2-0[2]cite-ref-3[3]

Contents

β€’ Signs and symptoms
β€’ Cause
β€’ Pathophysiology
β€’ Diagnosis
β€’ Treatment
β€’ History
β€’ See also
β€’ References
β€’ Further reading
β€’ External links

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Signs and symptoms

APS-1 tends to cause severe symptoms.cite-ref-1-4-0[4] These are present from early in life, usually around 3.5 years of age.cite-ref-1-4-1[4] Common symptoms of APS-1 include:

β€’ Chronic mucocutaneous candidiasis.cite-ref-1-4-2[4]
β€’ Hypoparathyroidism.cite-ref-1-4-3[4]
β€’ Addison's disease.cite-ref-1-4-4[4]
β€’ Ectodermal dystrophy (skin, dental enamel, and nails).

APS-1 may also cause:

β€’ Autoimmune hepatitis.cite-ref-1-4-5[4]
β€’ Hypogonadism.cite-ref-1-4-6[4]
β€’ Vitiligo.cite-ref-1-4-7[4]
β€’ Alopecia.cite-ref-1-4-8[4]
β€’ Malabsorption.
β€’ Pernicious anemia.
β€’ Cataract.
β€’ Cerebellar ataxia.cite-ref-2-5-0[5]

Cause

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.cite-ref-nih-1-1[1]cite-ref-nih2-2-1[2]cite-ref-6[6] The AIRE gene may be affected by any of at least 186 mutations.cite-ref-hgmd-7-0[7] APS-1 may be inherited in an autosomal recessive manner.cite-ref-pmid9837820-8-0[8]

Different mutations are more common in different geographic regions. R139X is a common mutation in Sardinia.cite-ref-1-4-9[4] R257* is a common mutation in Finland.cite-ref-2-5-1[5] Both of these mutations are nonsense mutations: the asterisk and the "X" both indicate a stop codon.cite-ref-hgmd-7-1[7] A 13-base-pair deletion in the AIRE gene, c.967-979del13bp, has been identified in APS-1 patients in Norway, Britaincite-ref-pmid9837820-8-1[8] and North America.cite-ref-9[9]cite-ref-10[10]

Pathophysiology

APS-1 is due to problems with immune tolerance.cite-ref-11[11] APS-1 causes considerable reactions with both interferon omega and interferon alpha.cite-ref-1-4-10[4]cite-ref-0-12-0[12] There may also be a reaction against interleukin 22.cite-ref-1-4-11[4] This leads to damage to endocrine organs.cite-ref-1-4-12[4] Common problems include hypercalcaemia and nephrocalcinosis (due to a lack of calcitonin from the thyroid), and pituitary problems (such as growth hormone deficiency).cite-ref-1-4-13[4] Antibodies against NLRP5 may lead to hypoparathyroidism.

Diagnosis

Diagnosis of APS-1 is based on a number of tests, including endoscopy, a CT scan,cite-ref-0-12-1[12] a biopsy (with histological testing),cite-ref-0-12-2[12] 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,cite-ref-pha-13-0[13] systemic antifungal treatments,cite-ref-1-4-14[4]cite-ref-pha-13-1[13] and immunosuppression.cite-ref-pha-13-2[13] The JAK-STAT inhibitor ruxolitinib is being investigated as a treatment specifically for its normalizing effect on interferon-gamma.cite-ref-14[14]

History

APS-1 may also be known as autoimmunity endocrinopathy candidiasis ectodermal dystrophy / dysplasia (APECED), autoimmune polyglandular syndrome type 1, Whitaker syndrome,cite-ref-0-12-3[12] or candidiasis-hypoparathyroidism-Addison's disease syndrome.cite-ref-greenspan-15-0[15]

See also

β€’ Autoimmune polyendocrine syndrome type 2
β€’ IPEX syndrome
β€’ Autoimmune polyendocrine syndrome

References

cite-note-nih-11. ↑ "AIRE gene". Genetics Home Reference. Archived from the original on 2017-04-05. Retrieved 2017-04-04.
cite-note-nih2-22. ↑ "APECED". Archived from the original on 2017-04-06. Retrieved 2017-04-04.
cite-note-33. ↑ citerefshoenfeldcerveragershwin2010Shoenfeld 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.
cite-note-1-44. ↑ citerefmeloniwillcoxmeageratzeni2012Meloni, 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.
cite-note-2-55. ↑ citereforlovasozaevakarevaoftedal2017Orlova, Elizaveta M; Sozaeva, Leila S; Kareva, Maria A; Oftedal, Bergithe E; Wolff, Anette S B; Breivik, Lars; Zakharova, Ekaterina Y; Ivanova, Olga N; KΓ€mpe, 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.
cite-note-66. ↑ "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.
cite-note-hgmd-77. ↑ citerefd-n-coopere-v-ballp-d-stensona-d-phillipsD.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.
cite-note-pmid9837820-88. ↑ citerefpearcecheethamimrievaidya1998Pearce 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.
cite-note-99. ↑ citerefbruserudoftedalwolffhusebye2016Bruserud 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.
cite-note-1010. ↑ citerefqianyanxuanzheng2022Qian 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.
cite-note-1111. ↑ citerefde-martinocapalboimprodad-elia2013De 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.
cite-note-0-1212. ↑ citerefaldasouqi2016Aldasouqi, 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.
cite-note-pha-1313. ↑ citerefinserm-reservedINSERM RESERVED. "Orphanet: Autoimmune polyendocrinopathy type 1". www.orpha.net. Archived from the original on 2017-04-23. Retrieved 2017-04-22.
cite-note-1414. ↑ citerefoikonomousmithconstantineschmitt2024Oikonomou, Vasileios; Smith, Grace; Constantine, Gregory M.; Schmitt, Monica M.; FerrΓ©, 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-Ξ³ 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.
cite-note-greenspan-1515. ↑ citerefgreenspangardner2004Greenspan, F. S.; Gardner, D. C. (2004). Basic clinical endocrinology. New York: McGraw-Hill. pp. 103. ISBN 978-0-07-140297-2.

Further reading

β€’ citerefde-martinocapalboimprodalorello2016De Martino L, Capalbo D, Improda N, Lorello P, Ungaro C, Di Mase R, et al. (1 January 2016). "Novel Findings into AIRE Genetics and Functioning: Clinical Implications". Frontiers in Pediatrics. 4: 86. doi:10.3389/fped.2016.00086. PMC 4992815. PMID 27597936.
β€’ citerefpetersonpitk-nensillanp-krohn2004Peterson P, PitkΓ€nen J, SillanpÀÀ N, Krohn K (March 2004). "Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED): a model disease to study molecular aspects of endocrine autoimmunity". Clinical and Experimental Immunology. 135 (3): 348–57. doi:10.1111/j.1365-2249.2004.02384.x. PMC 1808970. PMID 15008965.
β€’ citerefcapalbode-martinogiardinodi-mase2012Capalbo D, De Martino L, Giardino G, Di Mase R, Di Donato I, Parenti G, et al. (2012). "Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy: insights into genotype-phenotype correlation". International Journal of Endocrinology. 2012: 353250. doi:10.1155/2012/353250. PMC 3485503. PMID 23133448.

External links

β€’ PubMed

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