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]
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. [14]
In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". Prominent examples include celiac disease, diabetes mellitus type 1, Henoch–Schönlein purpura (HSP), systemic lupus erythematosus (SLE), Sjögren syndrome, eosinophilic granulomatosis with polyangiitis, Hashimoto's thyroiditis, Graves' disease, idiopathic thrombocytopenic purpura, Addison's disease, rheumatoid arthritis (RA), ankylosing spondylitis, polymyositis (PM), dermatomyositis (DM), and multiple sclerosis (MS). Autoimmune diseases are very often treated with steroids.
Addison's disease, also known as primary adrenal insufficiency, is a rare long-term endocrine disorder characterized by inadequate production of the steroid hormones cortisol and aldosterone by the two outer layers of the cells of the adrenal glands, causing adrenal insufficiency. Symptoms generally come on slowly and insidiously and may include abdominal pain and gastrointestinal abnormalities, weakness, and weight loss. Darkening of the skin in certain areas may also occur. Under certain circumstances, an adrenal crisis may occur with low blood pressure, vomiting, lower back pain, and loss of consciousness. Mood changes may also occur. Rapid onset of symptoms indicates acute adrenal failure, which is a clinical emergency. An adrenal crisis can be triggered by stress, such as from an injury, surgery, or infection.
Adrenal insufficiency is a condition in which the adrenal glands do not produce adequate amounts of steroid hormones. The adrenal glands—also referred to as the adrenal cortex—normally secrete glucocorticoids, mineralocorticoids, and androgens. These hormones are important in regulating blood pressure, electrolytes, and metabolism as a whole. Deficiency of these hormones leads to symptoms ranging from abdominal pain, vomiting, muscle weakness and fatigue, low blood pressure, depression, mood and personality changes to organ failure and shock. Adrenal crisis may occur if a person having adrenal insufficiency experiences stresses, such as an accident, injury, surgery, or severe infection; this is a life-threatening medical condition resulting from severe deficiency of cortisol in the body. Death may quickly follow.
Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that affect the patient's immune system. Examples of these extrinsic factors include HIV infection and environmental factors, such as nutrition. Immunocompromisation may also be due to genetic diseases/flaws such as SCID.
Autoimmune polyendocrine syndromes (APSs), also called polyglandular autoimmune syndromes (PGASs) or polyendocrine autoimmune syndromes (PASs), are a heterogeneous group of rare diseases characterized by autoimmune activity against more than one endocrine organ, although non-endocrine organs can be affected. There are three types of APS, and there are a number of other diseases which involve endocrine autoimmunity.
Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis and Hashimoto's disease, is an autoimmune disease in which the thyroid gland is gradually destroyed. A slightly broader term is autoimmune thyroiditis, identical other than that it is also used to describe a similar condition without a goiter.
FOXP3, also known as scurfin, is a protein involved in immune system responses. A member of the FOX protein family, FOXP3 appears to function as a master regulator of the regulatory pathway in the development and function of regulatory T cells. Regulatory T cells generally turn the immune response down. In cancer, an excess of regulatory T cell activity can prevent the immune system from destroying cancer cells. In autoimmune disease, a deficiency of regulatory T cell activity can allow other autoimmune cells to attack the body's own tissues.
Immunodysregulation polyendocrinopathy enteropathy X-linked syndrome is a rare autoimmune disease. It is one of the autoimmune polyendocrine syndromes. Most often, IPEX presents with autoimmune enteropathy, dermatitis (eczema), and autoimmune endocrinopathy, but other presentations exist.
Ectrodactyly–ectodermal dysplasia–cleft syndrome, or EEC, and also referred to as EEC syndrome and split hand–split foot–ectodermal dysplasia–cleft syndrome is a rare form of ectodermal dysplasia, an autosomal dominant disorder inherited as a genetic trait. EEC is characterized by the triad of ectrodactyly, ectodermal dysplasia, and facial clefts. Other features noted in association with EEC include vesicoureteral reflux, recurrent urinary tract infections, obstruction of the nasolacrimal duct, decreased pigmentation of the hair and skin, missing or abnormal teeth, enamel hypoplasia, absent punctae in the lower eyelids, photophobia, occasional cognitive impairment and kidney anomalies, and conductive hearing loss.
Immune dysregulation is any proposed or confirmed breakdown or maladaptive change in molecular control of immune system processes. For example, dysregulation is a component in the pathogenesis of autoimmune diseases and some cancers. Immune system dysfunction, as seen in IPEX syndrome leads to immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX). IPEX typically presents during the first few months of life with diabetes mellitus, intractable diarrhea, failure to thrive, eczema, and hemolytic anemia. unrestrained or unregulated immune response.
The autoimmune regulator (AIRE) is a protein that in humans is encoded by the AIRE gene. It is a 13kb gene on chromosome 21q22.3 that has 545 amino acids. AIRE is a transcription factor expressed in the medulla of the thymus. It is part of the mechanism which eliminates self-reactive T cells that would cause autoimmune disease. It exposes T cells to normal, healthy proteins from all parts of the body, and T cells that react to those proteins are destroyed.
Endocrine diseases are disorders of the endocrine system. The branch of medicine associated with endocrine disorders is known as endocrinology.
Hay–Wells syndrome is one of at least 150 known types of ectodermal dysplasia. These disorders affect tissues that arise from the ectodermal germ layer, such as skin, hair, and nails.
The enzyme sialate O-acetylesterase (EC 3.1.1.53) catalyzes the reaction
Autoimmune polyendocrine syndrome type 2, a form of autoimmune polyendocrine syndrome also known as APS-II, or PAS II, is the most common form of the polyglandular failure syndromes. PAS II is defined as the association between autoimmune Addison's disease and either autoimmune thyroid disease, type 1 diabetes, or both. It is heterogeneous and has not been linked to one gene. Rather, individuals are at a higher risk when they carry a particular human leukocyte antigen. APS-II affects women to a greater degree than men.
Autoimmune enteropathy is a rare autoimmune disorder characterized by weight loss from malabsorption, severe and protracted diarrhea, and autoimmune damage to the intestinal mucosa. Autoimmune enteropathy typically occurs in infants and younger children however, adult cases have been reported in literature. Autoimmune enteropathy was first described by Walker-Smith et al. in 1982.
Rajesh Vasantlal Thakker is May Professor of Medicine in the Nuffield Department of Clinical Medicine at the University of Oxford and a fellow of Somerville College, Oxford. Thakker is also a Consultant physician at the Churchill Hospital and the John Radcliffe Hospital, Principal investigator (PI) at the Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM) and was Chairman of the NIHR/MRC Efficacy and Mechanism Evaluation (EME) Board until Spring 2016.
Autoimmune polyendocrine syndrome, type 3 is characterized by the coexistence of two autoimmune illnesses, not including Addison's disease, and an autoimmune thyroid disease. Based on other organ-specific autoimmune involvement, there are multiple subtypes that are classified: type 3a shows thyroid autoimmune disease in conjunction with type 1 diabetes, type 3b shows thyroid autoimmune disease in conjunction with pernicious anemia (PA), and type 3c shows thyroid autoimmune disease in conjunction with alopecia, vitiligo, or other organ-specific autoimmune disease.
Autoimmune oophoritis is a rare autoimmune disease where the body's own immune system attacks the ovaries. This causes the ovaries to have inflammation, atrophy, and fibrosis. Such changes in the ovaries can cause them to not function properly. This disease is caused by primary ovarian insufficiency (POI), where reproduction and hormonal function of the ovaries stops before the age of 40.