Ectodermal dystrophy, candidiasis, autoimmune polyendocrinopathy -APECED- (Autoimmune polyendocrinopathy candidiasis-ectodermal dystrophy--APECED-) - Gen AIR

Ectodermal dystrophy, candidiasis, autoimmune polyendocrinopathy (APECED), also known as APS type 1 or type 1 autoimmune polyendocrinopathy syndrome is a hereditary disease that affects many organs. It is one of many autoimmune diseases that occur when the immune system does not function properly and mistakenly attacks its own organs and tissues. In most cases, the signs and symptoms of APECED begin in childhood or adolescence. This condition usually involves three characteristics: chronic mucocutaneous candidiasis (CMC), hypoparathyroidism and insufficiency of the adrenal glands. Affected individuals typically have at least two of these features, and many have three.

Chronic mucocutaneous candidiasis (CMC) is a tendency to develop skin infections, nails and mucous membranes caused by the fungus Candida spp. These infections are chronic, which means that resort and can last a long time. The CMC is usually the first of the three characteristic features of APECED. Likewise, almost all affected individuals develop canker sores. Esophageal infections are also common, while the skin and nails are less affected. In women, vaginal infections occur frequently.

Other features of APECED develop as a result of malfunction of the immune system that attacks the endocrine system. Damage to the parathyroid glands results in reducing the production of parathyroid hormone (hypoparathyroidism). Hypoparathyroidism may cause a tingling sensation in the lips, fingers and feet; muscle pain and cramping; weakness and fatigue. Furthermore, damage to the adrenals causes adrenal insufficiency (Addison 's disease). The reduced production of hormones by the adrenal glands leading to signs and symptoms may include fatigue (fatigue), muscle weakness, loss of appetite, weight loss, lower blood pressure and changes in skin color. Other endocrine problems that can occur in APECED include type 1 diabetes as a consequence of an alteration in the production of the hormone insulin; a deficiency of growth hormone resulting in short stature; problems affecting the ovaries or testes and can lead to infertility; and dysfunction of the thyroid gland, which may result in many symptoms, including weight gain and fatigue.

Autoimmune problems affecting non - endocrine tissues can lead to a variety of additional signs and symptoms. These features occur more frequently in populations in North America compared with European populations. Urticarial rashes are common and occur frequently in childhood and early childhood. Other signs and symptoms may include enamel hypoplasia and chronic diarrhea or constipation associated with difficulty absorbing nutrients from food. Additional features that occur, many of which may cause permanent damage to organs and tissues if not treated, including gastritis, hepatitis, pneumonitis, dry mouth and keratitis, nephritis, vitamin B12 deficiency, alopecia, vitiligo, hypertension or asplenia.

This process is due to mutations in the AIRE gene (regulatory autoimmune), located on the long arm of chromosome 21 (21q22.3), which encodes the regulatory protein called autoimmune. This protein is active primarily in the thymus. Thymus T cells prepared for its role in combating infection, a process known as thymic maturation. For a person to stay healthy cells of the immune system such as T cells, they must be able to identify and attack potentially harmful invaders (such as bacteria, fungi and viruses) while protecting normal tissues. Autoimmune regulatory protein plays an important role in this process, helping to distinguish T cells own proteins the body of foreign invaders. When this system is not working properly, the immune system 's ability to distinguish the body 's own proteins and foreign invaders is affected and can attack the tissues and organs themselves. Thymus, autoimmune regulatory protein destroys otherwise cause damage autoimmune T cells.

They have identified more than 90 mutations in the AIRE gene in people with ectodermal dystrophy, candidiasis, autoimmune polyendocrinopathy (APECED). Mutations AIRE gene responsible APECED development result in the synthesis of an abnormally short, nonfunctional version of the regulatory protein autoimmune or changing amino acids in critical regions of the protein. These mutations reduce or eliminate the function of autoimmune regulatory protein. Without enough functional protein, the ability to distinguish between immune body proteins and foreign invaders affect system and immune cells may attack organs themselves, leading to autoimmunity. This abnormal reaction causes inflammation and may damage other healthy cells and tissues. The autoimmune damage to the adrenal glands, the parathyroid glands and other organs underlies many of the main features of APECED.

Studies suggest that mutations AIRE gene also result in antibodies that mistakenly attack the proteins involved in an immunological process known as IL-17 pathway, which is important in the body's defense against Candida. This route, which relies on specialized proteins called cytokines IL-17 signaling leads to inflammation, additional cytokines and leukocytes to attack foreign invaders and promote tissue repair. In addition, IL-17 pathway promotes the production of peptides that control the growth of Candida in the surface of the mucous membranes. Damaging cytokines IL-17, it is believed that mutations in the AIRE gene impair the function of the IL-17 pathway, leading to chronic mucocutaneous candidiasis (CMC) in these people.

This disease is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease. In exceptional cases, people with a copy of certain mutations of the AIRE gene in every cell have some characteristics of APECED, as CMC, hypoparathyroidism or B12 deficiency, but do not have the complete pattern of signs and symptoms that generally characterize the disease. These individuals often have similarly affected parent.

Tests in IVAMI: in IVAMI perform detection of mutations associated with ectodermal dystrophy, candidiasis, autoimmune polyendocrinopathy (APECED), by complete PCR amplification of exons AIRE gene and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).