Autoimmune polyendocrine syndrome type 1

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]

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

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:

• Chronic mucocutaneous candidiasis.^[4]
• Hypoparathyroidism.^[4]
• Addison's disease.^[4]
• Ectodermal dystrophy (skin, dental enamel, and nails).

APS-1 may also cause:

• Autoimmune hepatitis.^[4]
• Hypogonadism.^[4]
• Vitiligo.^[4]
• Alopecia.^[4]
• Malabsorption.
• Pernicious anemia.
• Cataract.
• Cerebellar ataxia.^[5]

Cause

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

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

• Autoimmune polyendocrine syndrome type 2
• IPEX syndrome
• Autoimmune polyendocrine syndrome