Autoimmune polyendocrine syndrome type 1 (APS-1), is a subtype of

autoimmune polyendocrine syndrome 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 e ...

(autoimmune polyglandular syndrome). It causes the dysfunction of multiple endocrine glands due to

autoimmunity 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". ...

. It is a

genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...

, inherited in autosomal

recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

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: * Chronic mucocutaneous candidiasis. * Hypoparathyroidism. *

Addison's disease 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 ...

. * Ectodermal dystrophy (skin, dental enamel, and nails). APS-1 may also cause: *

Autoimmune hepatitis Autoimmune hepatitis, formerly known as lupoid hepatitis, plasma cell hepatitis, or autoimmune chronic active hepatitis, is a chronic, autoimmune disease of the liver that occurs when the body's immune system attacks liver cells, causing the li ...

. *

Hypogonadism Hypogonadism means diminished functional activity of the gonads—the testes or the ovaries—that may result in diminished production of sex hormones. Low androgen (e.g., testosterone) levels are referred to as hypoandrogenism and low estroge ...

. *

Vitiligo Vitiligo is a disorder that causes the skin to lose its color. Specific causes are unknown but studies suggest a link to immune system changes. Signs and symptoms The only sign of vitiligo is the presence of pale patchy areas of depigmen ...

. *

Alopecia Hair loss, also known as alopecia or baldness, refers to a loss of hair from part of the head or body. Typically at least the head is involved. The severity of hair loss can vary from a small area to the entire body. Inflammation or scarri ...

. *

Malabsorption Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal (GI) tract. Impairment can be of single or multiple nutrients depending on the abnormality. This may lead to malnutrition and a variety ...

. *

Pernicious anemia Pernicious anemia is a type of vitamin B12 deficiency anemia, a disease in which not enough red blood cells are produced due to the malabsorption of vitamin B12. Malabsorption in pernicious anemia results from the lack or loss of intrinsic f ...

. * Cataract. * Cerebellar ataxia.

Cause

Human male karyotpe high resolution - Chromosome 21 cropped

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 A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins ar ...

location, hence chromosome 21. The AIRE gene may be affected by any of at least 90

mutations In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitos ...

. Mutations may be inherited in an

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant an ...

manner. Different mutations are more common in different geographic regions. R139X is a common mutation in

Sardinia Sardinia ( ; it, Sardegna, label=Italian language, Italian, Corsican language, Corsican and Tabarchino ; sc, Sardigna , sdc, Sardhigna; french: Sardaigne; sdn, Saldigna; ca, Sardenya, label=Algherese dialect, Algherese and Catalan languag ...

. R257* is a common mutation in

Finland Finland ( fi, Suomi ; sv, Finland ), officially the Republic of Finland (; ), is a Nordic country in Northern Europe. It shares land borders with Sweden to the northwest, Norway to the north, and Russia to the east, with the Gulf of Bot ...

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 Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range is 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), with levels greater than 2.6 mmol/L defined as hypercalcemia ...

and nephrocalcinosis (due to a lack of

calcitonin Calcitonin is a 32 amino acid peptide hormone secreted by parafollicular cells (also known as C cells) of the thyroid (or endostyle) in humans and other chordates. in the ultimopharyngeal body. It acts to reduce blood calcium (Ca2+), opposing th ...

from the

thyroid The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The thy ...

), and pituitary problems (such as

growth hormone deficiency Growth hormone deficiency (GHD), or human growth hormone deficiency, is a medical condition resulting from not enough growth hormone (GH). Generally the most noticeable symptom is that an individual attains a short height. Newborns may also prese ...

). Antibodies against

NLRP5 NLRP5, short for NOD-like receptor family pyrin domain containing 5, is an intracellular protein that plays a role in early embryogenesis. NLRP5 is also known as NACHT, LRR and PYD domains-containing protein 5 (NALP5), Mater protein homolog (MA ...

may lead to hypoparathyroidism.

Diagnosis

Diagnosis of APS-1 is based on a number of tests, including endoscopy, a CT scan, a biopsy (with histological testing), 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 An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as cryp ...

treatments, and

immunosuppression Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reacti ...

History

APS-1 may also be known as autoimmunity endocrinopathy candidiasis ectodermal dystrophy / dysplasia (APECED), autoimmune polyglandular syndrome type 1, Whitaker syndrome, or candidiasis-hypoparathyroidism-Addison's disease syndrome.

References

External links

PubMed
{{Transcription factor deficiencies Endocrine diseases Autoimmune diseases Transcription factor deficiencies Syndromes