Autoimmune polyendocrine syndrome type 1


Autoimmune polyendocrine syndrome type 1, is a subtype of autoimmune polyendocrine 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:
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, and pituitary problems. 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, 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, autoimmune polyglandular syndrome type 1, Whitaker syndrome, or candidiasis-hypoparathyroidism-Addison's disease syndrome.