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Immunoendocrinology: Scientific and Clinical Aspects pp 115–128Cite as

Autoimmune Polyendocrine Syndrome Type I: Man

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Part of the book series: Contemporary Endocrinology ((COE))

Summary

Autoimmune polyendocrine syndrome type I (APS-I) is a monogenic disease with the three main components: chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency. In addition, a number of other endocrine, gastrointestinal, and ectodermal tissues are targeted. There is a huge variability in clinical phenotype, but in typical cases main components appear in childhood and adolescence. The main diagnostic criterion is still the presence of two of the three main components, but diagnosis can be aided by the mutational analysis of the autoimmune regulator (AIRE) gene and assay of specific autoantibodies, particularly against interferon omega and alpha. Many patients are diagnosed late or not at all, and the management is not optimal. An overview of the main clinical aspects, diagnostic approaches, and treatment will hopefully contribute to improved care for APS-I patients.

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References

  1. Ahonen P, Myllarniemi S, Sipila I, Perheentupa J. Clinical variation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in a series of 68 patients. N Engl J Med 1990;322(26):1829–1836.

    Article  PubMed  CAS  Google Scholar 

  2. Betterle C, Greggio NA, Volpato M. Clinical review 93: Autoimmune polyglandular syndrome type 1. J Clin Endocrinol Metab 1998;83(4):1049–1055.

    Article  PubMed  CAS  Google Scholar 

  3. Perheentupa J: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. J Clin Endocrinol Metab 2006;91(8):2843–2850.

    Article  PubMed  CAS  Google Scholar 

  4. Wolff AS, Erichsen MM, Meager A, et al. Autoimmune polyendocrine syndrome type 1 in Norway: phenotypic variation, autoantibodies, and novel mutations in the autoimmune regulator gene. J Clin Endocrinol Metab 2007;92(2):595–603.

    Article  PubMed  CAS  Google Scholar 

  5. Rosatelli MC, Meloni A, Devoto M, et al. A common mutation in Sardinian autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients. Hum Genet 1998;103(4):428–434.

    Article  PubMed  CAS  Google Scholar 

  6. Zlotogora J, Shapiro MS. Polyglandular autoimmune syndrome type I among Iranian Jews. J Med Genet 1992;29(11):824–826.

    Article  PubMed  CAS  Google Scholar 

  7. Alimohammadi M, Bjorklund P, Hallgren A, et al. Autoimmune polyendocrine syndrome type 1 and NALP5, a parathyroid autoantigen. N Engl J Med 2008;358(10):1018–1028.

    Article  PubMed  CAS  Google Scholar 

  8. Ekwall O, Hedstrand H, Grimelius L, et al. Identification of tryptophan hydroxylase as an intestinal autoantigen. Lancet 1998;352(9124):279–283.

    Article  PubMed  CAS  Google Scholar 

  9. Meager A, Visvalingam K, Peterson P, et al. Anti-interferon autoantibodies in autoimmune polyendocrinopathy syndrome type 1. PLoS Med 2006;3(7):e289.

    Article  PubMed  Google Scholar 

  10. Meloni A, Furcas M, Cetani F, et al. Autoantibodies against type I interferons as an additional diagnostic criterion for autoimmune polyendocrine syndrome type I. J Clin Endocrinol Metab 2008;93(11):4389–4397.

    Article  PubMed  CAS  Google Scholar 

  11. Finnish-German APECED Consortium. Autoimmune polyendocrinopathy-Candidiasis-Ectodermal Dystrophy. An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. Nat Genet 1997;17(4):399–403.

    Article  Google Scholar 

  12. Nagamine K, Peterson P, Scott HS, et al. Positional cloning of the APECED gene. Nat Genet 1997;17(4):393–398.

    Article  PubMed  CAS  Google Scholar 

  13. Trebusak Podkrajsek K, Milenkovic T, Odink R, et al. Detection of a complete AIRE gene deletion and two additional novel mutations in a cohort of patients with atypical phenotypic variants of APS-1. Eur J Endocrinol 2008;159(5):633–639.

    Google Scholar 

  14. Winer KK, Sinaii N, Peterson D, Sainz B, Jr., Cutler GB, Jr. Effects of once versus twice-daily parathyroid hormone 1-34 therapy in children with hypoparathyroidism. J Clin Endocrinol Metab 2008;93(9):3389–3395.

    Article  PubMed  CAS  Google Scholar 

  15. Söderbergh A, Myhre AG, Ekwall O, et al. Prevalence and clinical associations of 10 defined autoantibodies in autoimmune polyendocrine syndrome type I. J Clin Endocrinol. Metab 2004;89(2):557–562.

    Article  PubMed  Google Scholar 

  16. Mah PM, Jenkins RC, Rostami-Hodjegan A, et al. Weight-related dosing, timing and monitoring hydrocortisone replacement therapy in patients with adrenal insufficiency. Clin Endocrinol (Oxf) 2004;61(3):367–375.

    Article  CAS  Google Scholar 

  17. Neufeld M, Maclaren NK, Blizzard RM. Two types of autoimmune Addison’s disease associated with different polyglandular autoimmune (PGA) syndromes. Medicine (Baltimore) 1981;60(5):355–362.

    Article  CAS  Google Scholar 

  18. Cetani F, Barbesino G, Borsari S, et al. A novel mutation of the autoimmune regulator gene in an Italian kindred with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, acting in a dominant fashion and strongly cosegregating with hypothyroid autoimmune thyroiditis. J Clin Endocrinol Metab 2001;86(10):4747–4752.

    Article  PubMed  CAS  Google Scholar 

  19. Su MA, Giang K, Zumer K, et al. Mechanisms of an autoimmunity syndrome in mice caused by a dominant mutation in Aire. J Clin Invest 2008;118(5):1712–1726.

    Article  PubMed  CAS  Google Scholar 

  20. Perheentupa J. APS-I/APECED: the clinical disease and therapy. Endocrinol Metab Clin North Am 2002;31(2):295–320, vi.

    Article  Google Scholar 

  21. Rautemaa R, Hietanen J, Niissalo S, Pirinen S, Perheentupa J. Oral and oesophageal squamous cell carcinoma – a complication or component of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, APS-I). Oral Oncol 2007;43(6):607–613.

    Article  PubMed  Google Scholar 

  22. Rautemaa R, Richardson M, Pfaller M, Perheentupa J, Saxen H. Reduction of fluconazole susceptibility of Candida albicans in APECED patients due to long-term use of ketoconazole and miconazole. Scand J Infect Dis 2008;23:1–4.

    Google Scholar 

  23. Gebre-Medhin G, Husebye ES, Gustafsson J, et al. Cytochrome P450IA2 and aromatic L-amino acid decarboxylase are hepatic autoantigens in autoimmune polyendocrine syndrome type I. FEBS Lett 1997;412(3): 439–445.

    Article  PubMed  CAS  Google Scholar 

  24. Obermayer-Straub P, Perheentupa J, Braun S, et al. Hepatic autoantigens in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Gastroenterology 2001;121(3):668–677.

    Article  PubMed  CAS  Google Scholar 

  25. Ward L, Paquette J, Seidman E, et al. Severe autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy in an adolescent girl with a novel AIRE mutation: response to immunosuppressive therapy. J Clin Endocrinol Metab 1999;84(3):844–852.

    Article  PubMed  CAS  Google Scholar 

  26. Bereket A, Lowenheim M, Blethen SL, Kane P, Wilson TA. Intestinal lymphangiectasia in a patient with autoimmune polyglandular disease type I and steatorrhea. J Clin Endocrinol Metab 1995;80(3):933–935.

    Article  PubMed  CAS  Google Scholar 

  27. Makharia GK, Tandon N, Stephen Nde J, Gupta SD, Tandon RK: Primary intestinal lymphangiectasia as a component of autoimmune polyglandular syndrome type I: a report of 2 cases. Indian J Gastroenterol 2007;26(6):293–295.

    PubMed  Google Scholar 

  28. Merenmies L, Tarkkanen A. Chronic bilateral keratitis in autoimmune polyendocrinopathy-candidiadis-ectodermal dystrophy (APECED). A long-term follow-up and visual prognosis. Acta Ophthalmol Scand 2000;78(5): 532–535.

    Article  PubMed  CAS  Google Scholar 

  29. Chang B, Brosnahan D, McCreery K, Dominguez M, Costigan C. Ocular complications of autoimmune polyendocrinopathy syndrome type 1. J AAPOS 2006;10(6):515–520.

    Article  PubMed  Google Scholar 

  30. Tarkkanen A, Merenmies L. Corneal pathology and outcome of keratoplasty in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Acta Ophthalmol Scand 2001;79(2):204–207.

    Article  PubMed  CAS  Google Scholar 

  31. Shah M, Holland E, Chan CC. Resolution of autoimmune polyglandular syndrome-associated keratopathy with keratolimbal stem cell transplantation: case report and historical literature review. Cornea 2007;26(5):632–635.

    PubMed  Google Scholar 

  32. Perniola R, Tamborrino G, Marsigliante S, De Rinaldis C. Assessment of enamel hypoplasia in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). J Oral Pathol Med 1998;27(6):278–282.

    Article  PubMed  CAS  Google Scholar 

  33. Ulinski T, Perrin L, Morris M, et al. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome with renal failure: impact of posttransplant immunosuppression on disease activity. J Clin Endocrinol Metab 2006;91(1):192–195.

    Article  PubMed  CAS  Google Scholar 

  34. Bensing S, Fetissov SO, Mulder J, et al. Pituitary autoantibodies in autoimmune polyendocrine syndrome type 1. Proc Natl Acad Sci U S A 2007;104(3):949–954.

    Article  PubMed  CAS  Google Scholar 

  35. De Luca F, Valenzise M, Alaggio R, et al. Sicilian family with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) and lethal lung disease in one of the affected brothers. Eur J Pediatr 2008; 167(11):1283–1288.

    Article  PubMed  Google Scholar 

  36. Jiang W, Anderson MS, Bronson R, Mathis D, Benoist C. Modifier loci condition autoimmunity provoked by Aire deficiency. J Exp Med 2005;202(6):805–815.

    Article  PubMed  CAS  Google Scholar 

  37. Harris M, Kecha O, Deal C, et al. Reversible metaphyseal dysplasia, a novel bone phenotype, in two unrelated children with autoimmunepolyendocrinopathy-candidiasis-ectodermal dystrophy: clinical and molecular studies. J Clin Endocrinol Metab 2003;88(10):4576–4585.

    Article  PubMed  CAS  Google Scholar 

  38. Evans RA, Carter JN, Shenston B, et al. Candidiasis-endocrinopathy syndrome with progressive myopathy. Q J Med 1989;70(262):139–144.

    PubMed  CAS  Google Scholar 

  39. Oftedal BE, Wolff AS, Bratland E, et al. Radioimmunoassay for autoantibodies against interferon omega; its use in the diagnosis of autoimmune polyendocrine syndrome type I. Clin Immunol 2008;129(1):163–169.

    Article  PubMed  CAS  Google Scholar 

  40. Myhre AG, Halonen M, Eskelin P, et al. Autoimmune polyendocrine syndrome type 1 (APS I) in Norway. Clin Endocrinol (Oxf) 2001;54(2):211–217.

    Article  CAS  Google Scholar 

  41. Bensing S, Brandt L, Tabaroj F, et al. Increased death risk and altered cancer incidence pattern in patients with isolated or combined autoimmune primary adrenocortical insufficiency. Clin Endocrinol (Oxf) 2008;69(5):697–704.

    Article  Google Scholar 

  42. Anderson MS, Venanzi ES, Klein L, et al. Projection of an immunological self shadow within the thymus by the aire protein. Science 2002;298(5597):1395–1401.

    Article  PubMed  CAS  Google Scholar 

  43. Liston A, Lesage S, Wilson J, Peltonen L, Goodnow CC. Aire regulates negative selection of organ-specific T cells. Nat Immunol 2003;4(4):350–354.

    Article  PubMed  CAS  Google Scholar 

  44. Gardner JM, Devoss JJ, Friedman RS, et al. Deletional tolerance mediated by extrathymic Aire-expressing cells. Science 2008;321(5890):843–847.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The work was supported by The European Union FP 6 research project EurAPS, The Swedish Research Council, The Norwegian Research Council, and The Western Regional Health Authorities, Norway.

Conflict of interest: None declared.

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Authors and Affiliations

  1. Department of Medicine, Institute of Medicine, Haukeland University Hospital, University of Bergen, Bergen, Norway

    Eystein S. Husebye

  2. Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden

    Olle Kämpe

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  1. Eystein S. Husebye
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Editors and Affiliations

  1. Health Sciences Center, Children's Hospital, University of Colorado, East 9th Avenue 4200, Denver, 80262, Colorado, USA

    George S. Eisenbarth

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Husebye, E.S., Kämpe, O. (2011). Autoimmune Polyendocrine Syndrome Type I: Man. In: Eisenbarth, G. (eds) Immunoendocrinology: Scientific and Clinical Aspects. Contemporary Endocrinology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-478-4_7

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  • DOI: https://doi.org/10.1007/978-1-60327-478-4_7

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  • Publisher Name: Humana Press, Totowa, NJ

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