Autoimmune polyendocrine syndrome type 1

(Redirected from APECED) Autoimmune condition causing dysfunction of endocrine glands Medical condition

Autoimmune polyendocrine syndrome type 1
Other names	Autoimmune 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
Specialty	Endocrinology, medical genetics
Symptoms	chronic mucocutaneous candidiasis
Causes	mutation 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.

Signs and symptoms

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

Chronic mucocutaneous candidiasis.
Hypoparathyroidism.
Addison's disease.
Ectodermal dystrophy (skin, dental enamel, and nails).

APS-1 may also cause:

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. The AIRE gene may be affected by any of at least 186 mutations. APS-1 may be inherited in an autosomal recessive manner.

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

Pathophysiology

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

Diagnosis

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

History

APS-1 may also be known as autoimmunity endocrinopathy candidiasis ectodermal dystrophy / dysplasia (APECED), autoimmune polyglandular syndrome type 1, Whitaker syndrome, or candidiasis-hypoparathyroidism-Addison's disease syndrome.

References

^ "AIRE gene". Genetics Home Reference. Archived from the original on 2017-04-05. Retrieved 2017-04-04.
^ "APECED". Archived from the original on 2017-04-06. Retrieved 2017-04-04.
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.
^ 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.
^ 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.
"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.
^ 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.
^ 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.
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.
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.
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.
^ 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.
^ INSERM RESERVED. "Orphanet: Autoimmune polyendocrinopathy type 1". www.orpha.net. Archived from the original on 2017-04-23. Retrieved 2017-04-22.
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.
Greenspan, F. S.; Gardner, D. C. (2004). Basic clinical endocrinology. New York: McGraw-Hill. pp. 103. ISBN 978-0-07-140297-2.

External links

PubMed

Classification	D ICD-10: E31.0 ICD-9-CM: 258.1 OMIM: 240300 MeSH: D016884 DiseasesDB: 29212
External resources	eMedicine: med/1867 Orphanet: 3453

Scholia has a topic profile for Autoimmune polyendocrine syndrome type 1.

v t e Disorders involving multiple endocrine glands
Autoimmune polyendocrine syndrome APS1 APS2 Carcinoid syndrome Multiple endocrine neoplasia 1 2A 2B Progeria Werner syndrome Acrogeria Metageria Woodhouse–Sakati syndrome

Hypersensitivity and autoimmune diseases

Type I/allergy/atopy
(IgE)

Foreign	Allergic asthma Allergic urticaria Allergic rhinitis (Hay fever) Anaphylaxis Atopic dermatitis Food allergy common allergies include: Egg Milk Peanut Seafood Soy Tree nut Wheat Penicillin allergy
Autoimmune	Autoimmune urticaria Eosinophilic esophagitis

Type II/ADCC

- IgG
- IgM

Foreign

Hemolytic disease of the newborn

Autoimmune

Cytotoxic	Autoimmune hemolytic anemia Bullous pemphigoid Goodpasture syndrome Guillain–Barré syndrome Immune thrombocytopenic purpura Pemphigus vulgaris Rheumatic fever
"Type V"/receptor	Graves' disease Myasthenia gravis Pernicious anemia

Type III
(Immune complex)

Foreign	Arthus reaction Farmer's lung Henoch–Schönlein purpura Hypersensitivity vasculitis Post-streptococcal glomerulonephritis Reactive arthritis Serum sickness
Autoimmune	Lupus Rheumatoid arthritis Subacute bacterial endocarditis

Type IV/cell-mediated
(T cells)

Foreign	Allergic contact dermatitis Mantoux test
Autoimmune	Coeliac disease Giant cell arteritis Hashimoto's thyroiditis Multiple sclerosis Postorgasmic illness syndrome Reactive arthritis Type 1 diabetes
GVHD	Transfusion-associated graft-versus-host disease

Unknown/
multiple

Foreign	Hypersensitivity pneumonitis Allergic bronchopulmonary aspergillosis Latex allergy (I+IV) Transplant rejection
Autoimmune	Autoimmune adrenalitis Autoimmune hepatitis Autoimmune polyendocrine syndrome APS1 APS2 Sjögren syndrome Systemic autoimmune disease

Genetic disorders relating to deficiencies of transcription factor or coregulators

(1) Basic domains

1.2	Feingold syndrome Saethre–Chotzen syndrome
1.3	Tietz syndrome

(2) Zinc finger
DNA-binding domains

2.1	(Intracellular receptor): Thyroid hormone resistance Androgen insensitivity syndrome PAIS MAIS CAIS Kennedy's disease PHA1AD pseudohypoaldosteronism Estrogen insensitivity syndrome X-linked adrenal hypoplasia congenita MODY 1 Familial partial lipodystrophy 3 SF1 XY gonadal dysgenesis
2.2	Barakat syndrome Tricho–rhino–phalangeal syndrome
2.3	Greig cephalopolysyndactyly syndrome/Pallister–Hall syndrome Denys–Drash syndrome Duane-radial ray syndrome MODY 7 MRX 89 Townes–Brocks syndrome Acrocallosal syndrome Myotonic dystrophy 2
2.5	Autoimmune polyendocrine syndrome type 1

(3) Helix-turn-helix domains

3.1	ARX Ohtahara syndrome Lissencephaly X2 MNX1 Currarino syndrome HOXD13 SPD1 synpolydactyly PDX1 MODY 4 LMX1B Nail–patella syndrome MSX1 Tooth and nail syndrome OFC5 PITX2 Axenfeld syndrome 1 POU4F3 DFNA15 POU3F4 DFNX2 ZEB1 Posterior polymorphous corneal dystrophy Fuchs' dystrophy 3 ZEB2 Mowat–Wilson syndrome
3.2	PAX2 Papillorenal syndrome PAX3 Waardenburg syndrome 1&3 PAX4 MODY 9 PAX6 Gillespie syndrome Coloboma of optic nerve PAX8 Congenital hypothyroidism 2 PAX9 STHAG3
3.3	FOXC1 Axenfeld syndrome 3 Iridogoniodysgenesis, dominant type FOXC2 Lymphedema–distichiasis syndrome FOXE1 Bamforth–Lazarus syndrome FOXE3 Anterior segment mesenchymal dysgenesis FOXF1 ACD/MPV FOXI1 Enlarged vestibular aqueduct FOXL2 Premature ovarian failure 3 FOXP3 IPEX
3.5	IRF6 Van der Woude syndrome Popliteal pterygium syndrome

(4) β-Scaffold factors
with minor groove contacts

4.2	Hyperimmunoglobulin E syndrome
4.3	Holt–Oram syndrome Li–Fraumeni syndrome Ulnar–mammary syndrome
4.7	Campomelic dysplasia MODY 3 MODY 5 SF1 SRY XY gonadal dysgenesis Premature ovarian failure 7 SOX10 Waardenburg syndrome 4c Yemenite deaf-blind hypopigmentation syndrome
4.11	Cleidocranial dysostosis

(0) Other transcription factors

0.6	Kabuki syndrome

Ungrouped

Transcription coregulators

Coactivator:	CREBBP Rubinstein–Taybi syndrome
Corepressor:	HR (Atrichia with papular lesions)

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