Autoimmune polyendocrine syndrome type 1 | |
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Other names | Autoimmune polyendocrinopathy-candidiasis–ectodermal dystrophy/dysplasia (APECED), Autoimmune polyglandular syndrome type 1, Whitaker syndrome, Contents
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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. [1] [2] [3]
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:
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]
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 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.
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]
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]