Autoimmune polyendocrine syndrome type 1

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Autoimmune polyendocrine syndrome type 1
Other namesAutoimmune polyendocrinopathy-candidiasis–ectodermal dystrophy/dysplasia (APECED),

Autoimmune polyglandular syndrome type 1, Whitaker syndrome,

Contents

Candidiasis-hypoparathyroidism–Addison's disease syndrome
Autosomal recessive - en.svg
Autoimmune polyendocrine syndrome type 1 is autosomal recessive
Specialty Endocrinology, medical genetics
Symptoms chronic mucocutaneous candidiasis
Causesmutation in AIRE gene
Diagnostic method CT scan, biopsy
Treatment hormone 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

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

Chromosome 21 Human male karyotpe high resolution - Chromosome 21 cropped.png
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

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

Endoscope Flexibles Endoskop.jpg
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

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

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

References

  1. 1 2 "AIRE gene". Genetics Home Reference. Archived from the original on 2017-04-05. Retrieved 2017-04-04.
  2. 1 2 "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. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 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.
  5. 1 2 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.
  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. 1 2 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. 1 2 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.
  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.
  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. 1 2 3 4 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. 1 2 3 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.
  15. ↑ Greenspan, F. S.; Gardner, D. C. (2004). Basic clinical endocrinology . New York: McGraw-Hill. pp.  103. ISBN   978-0-07-140297-2.

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