Autoimmune polyendocrine syndrome type 1 symptoms and signs include the following:

- Hypoparathyroidism

- Hypogonadism

- Vitiligo

- Alopecia

- Malabsorption

- Anemia

- Cataract

- Adrenal hyperplasia

Autoimmune polyendocrine syndrome type 1 (APS-1), also known as autoimmune polyendocrinopathy-candidiasis–ectodermal dystrophy/dysplasia (APECED), autoimmune polyglandular syndrome type 1, Whitaker syndrome, or candidiasis-hypoparathyroidism–Addison's disease syndrome, is a subtype of autoimmune polyendocrine syndrome (autoimmune polyglandular syndrome) in which multiple endocrine glands dysfunction as a result of 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.

Symptoms(and signs) that are consistent with this disorder are the following:

Autoimmune polyendocrine syndromes (APS) occur when more than one autoimmune disease occurs in endocrine glands. These syndromes are also called Polyendocrine Autoimmune Disorders. In Type 3, autoimmune thyroiditis and another endocrine autoimmune disease are present, but the adrenal cortex is not involved.

Autoimmune polyendocrine syndrome type 2, a form of autoimmune polyendocrine syndrome also known as Schmidt's syndrome, or APS-II, is the most common form of the polyglandular failure syndromes. 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 (HLA-DQ2, HLA-DQ8 and HLA-DR4). APS-II affects women to a greater degree than men.

Autoimmune polyendocrine syndromes (APSs), also called autoimmune polyglandular syndromes (APSs), polyglandular autoimmune syndromes (PGASs), or polyendocrine autoimmune syndromes, 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 or (in terms that mean the same thing) three APSs, and there are a number of other diseases which have endocrine autoimmunity.

For this condition, differential diagnosis sees that the following should be considered:

- CD25 deficiency

- STAT5b deficiency

- Severe immunodeficiency(combined)

- X-linked thrombocytopenia

The bare lymphocyte syndrome, type II (BLS II) is a rare recessive genetic condition in which a group of genes called major histocompatibility complex class II (MHC class II) are not expressed.

The result is that the immune system is severely compromised and cannot effectively fight infection. Clinically, this is similar to severe combined immunodeficiency (SCID), in which lymphocyte precursor cells are improperly formed. As a notable contrast, however, bare lymphocyte syndrome does not result in decreased B- and T-cell counts, as the development of these cells is not impaired.

Diarrhea can be among the associated conditions.

Bare lymphocyte syndrome is a condition caused by mutations in certain genes of the major histocompatibility complex or involved with the processing and presentation of MHC molecules. It is a form of severe combined immunodeficiency.

Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) is listed as a "rare disease" by the Office of Rare Diseases (ORD) of the National Institutes of Health (NIH). This means that MOPD, or a subtype of MOPD, affects less than 200,000 people in the US population and a form of dwarfism associated with brain and skeletal abnormalities.

It was characterized in 1982.

It is associated with "PCNT".

Types II and III (or mixed or variant) cryoglobulinemic disease may also present with symptoms and signs of blood hyperviscosity and intravascular cryoglobulin deposition but also include those attributable to cryoglobulinemic vasculitis. "Meltzer's triad" of palpable purpura, joint pain, and generalized weakness occurs in ~33% of patients presenting with type II or type III disease. One or more skin lesions including palpable purpura, ulcers, digital gangrene, and areas of necrosis occur in 69-89% of these mixed disease cases (see attached photograph); less common findings include painful peripheral neuropathy (19-44% of cases), kidney disease (primarily membranoproliferative glomerulonephritis (30%), joint pain (28%), and, less commonly, dry eye syndrome, Raynaud phenomenon (i.e. episodic painful reductions in blood flow to the fingers and toes). While the glomerulonephritis occurring in mixed disease appears to be due to inflammatory vasculitis, the glomerulonephritis occurring in type I disease appears due to the interruption of blood flow. The hematological, infectious, and autoimmune diseases underlying type II cryoglobulinemic disease and the infectious and autoimmune diseases underlying type III cryoglobulinemic disease are also critical parts of the disease's clinical findings.

Signs and symptoms due to the cryoglobulins of type I disease reflect the hyperviscosity and deposition of cryoglobulins within the blood vessels which reduce or stop blood perfusion to tissues. These events occur particularly in cases where blood cryoglobulin levels of monoclonal IgM are high in patients with IgM MGUS, smoldering Waldenström's macroglobulinemia, or Waldenström's macroglobulinemia and in uncommon cases where the levels of monoclonal IgA, IgG, free κ light chains, or free λ light chains are extremely high in patients with non-IgM MGUS, non-IgM smoldering multiple myeloma, or multiple myeloma. The interruption of blood flow to neurological tissues can cause symptoms of confusion, headache, hearing loss, and peripheral neuropathy. Interruption of blood flow to other tissues in type I disease can cause cutaneous manifestations of purpura, acrocyanosis, necrosis, ulcers, and livedo reticularis; spontaneous nose bleeds, joint pain, membranoproliferative glomerulonephritis; and cardiovascular disturbances such as shortness of breath, hypoxemia, and congestive heart failure.

Genetic changes are related to the following types of collagenopathy, types II and XI.

The system for classifying collagenopathies is changing as researchers learn more about the genetic causes of these disorders.The clinical features of the type II and XI collagenopathies vary among the disorders, but there is considerable overlap. Common signs and symptoms include problems with bone development that can result in short stature, enlarged joints, spinal curvature, and arthritis at a young age. For some people, bone changes can be seen only on X-ray images. Problems with vision and hearing, as well as a cleft palate with a small lower jaw, are common. Some individuals with these disorders have distinctive facial features such as protruding eyes and a flat nasal bridge.

Type II tyrosinemia is caused by a deficiency of the enzyme tyrosine aminotransferase (), encoded by the gene "TAT". Tyrosine aminotransferase is the first in a series of five enzymes that converts tyrosine to smaller molecules, which are excreted by the kidneys or used in reactions that produce energy. This form of the disorder can affect the eyes, skin, and mental development. Symptoms often begin in early childhood and include excessive tearing, abnormal sensitivity to light (photophobia), eye pain and redness, and painful skin lesions on the palms and soles. About half of individuals with type II tyrosinemia are also mentally challenged. Type II tyrosinemia occurs in fewer than 1 in 250,000 individuals.

Tyrosinemia type II (Oculocutaneous tyrosinemia, Richner-Hanhart syndrome) is an autosomal recessive condition with onset between ages 2 and 4 years, when painful circumscribed calluses develop on the pressure points of the palm of the hand and sole of the foot.

The type II and XI collagenopathies are a group of disorders that affect connective tissue, the tissue that supports the body's joints and organs. These disorders are caused by defects in type II or type XI collagen. Collagens are complex molecules that provide structure, strength, and elasticity to connective tissue. Type II and type XI collagen disorders are grouped together because both types of collagen are components of the cartilage found in joints and the spinal column, the inner ear, and the jelly-like substance that fills the eyeball (the vitreous). The type II and XI collagenopathies result in similar clinical features.

Antiphospholipid syndrome or antiphospholipid antibody syndrome (APS or APLS), is an autoimmune, hypercoagulable state caused by antiphospholipid antibodies. APS provokes blood clots (thrombosis) in both arteries and veins as well as pregnancy-related complications such as miscarriage, stillbirth, preterm delivery, and severe preeclampsia.

The diagnostic criteria require one clinical event (i.e. thrombosis or pregnancy complication) and two antibody blood tests spaced at least three months apart that confirm the presence of either lupus anticoagulant or anti-β-glycoprotein-I (since β-glycoprotein-I antibodies are a subset of anti-cardiolipin antibodies, an anti-cardiolipin assay can be performed as a less specific proxy).

Antiphospholipid syndrome can be primary or secondary. Primary antiphospholipid syndrome occurs in the absence of any other related disease. Secondary antiphospholipid syndrome occurs with other autoimmune diseases, such as systemic lupus erythematosus (SLE). In rare cases, APS leads to rapid organ failure due to generalised thrombosis; this is termed "catastrophic antiphospholipid syndrome" (CAPS or Asherson syndrome) and is associated with a high risk of death.

Antiphospholipid syndrome often requires treatment with anticoagulant medication such as heparin to reduce the risk of further episodes of thrombosis and improve the prognosis of pregnancy. Warfarin/Coumadin is not used during pregnancy because it can cross the placenta, unlike heparin, and is teratogenic.

Symptoms vary from one type of the syndrome to another and from one patient to another, but they include:

- Very pale or brilliantly blue eyes, eyes of two different colors (complete heterochromia), or eyes with one iris having two different colors (sectoral heterochromia)

- A forelock of white hair ("poliosis"), or premature graying of the hair

- Appearance of wide-set eyes due to a prominent, broad nasal root ("dystopia canthorum")—particularly associated with Type I) also known as "telecanthus"

- Moderate to profound hearing loss (higher frequency associated with Type II);

- A low hairline and eyebrows that meet in the middle ("synophrys")

- Patches of white skin pigmentation, in some cases

- Abnormalities of the arms, associated with Type III

- neurologic manifestations, associated with Type IV

- Cleft lip, mostly associated with Type I

Waardenburg syndrome has also been associated with a variety of other congenital disorders, such as intestinal and spinal defects, elevation of the scapula and cleft lip and palate. Sometimes this is concurrent with Hirschsprung disease.

The specific problems produced differ according to the particular abnormal synthesis involved. Common manifestations include ataxia; seizures; retinopathy; liver fibrosis; coagulopathies; failure to thrive; dysmorphic features ("e.g.," inverted nipples and subcutaneous fat pads; and strabismus. If an MRI is obtained, cerebellar atrophy and hypoplasia is a common finding.

Ocular abnormalities of CDG-Ia include: myopia, infantile esotropia, delayed visual maturation, low vision, optic disc pallor, and reduced rod function on electroretinography.

Three subtypes of CDG I (a,b,d) can cause congenital hyperinsulinism with hyperinsulinemic hypoglycemia in infancy.

The presence of antiphospholipid antibodies (aPL) in the absence of blood clots or pregnancy-related complications does not indicate APS (see below for the diagnosis of APS).

Antiphospholipid syndrome can cause arterial or venous blood clots, in any organ system, or pregnancy-related complications. In APS patients, the most common venous event is deep vein thrombosis of the lower extremities, and the most common arterial event is stroke. In pregnant women affected by APS, there is an increased risk of recurrent miscarriage, intrauterine growth restriction, and preterm birth. A frequent cause of such complications is placental infarctions.

In some cases, APS seems to be the leading cause of mental and/or development retardation in the newborn, due to an aPL-induced inhibition of trophoblast differentiation. The antiphospholipid syndrome responsible for most of the miscarriages in later trimesters seen in concomitant systemic lupus erythematosus and pregnancy.

Other common findings, although not part of the APS classification criteria, are low platelet count, heart valve disease, and livedo reticularis. There are also associations between antiphospholipid antibodies and headaches, migraines, and oscillopsia. Some studies have shown the presence of antiphospholipid antibodies in the blood and spinal fluid of patients with psychological symptoms.

Very few patients with primary APS go on to develop SLE.

Mutations in several genes have been associated with the traditional clinical syndromes, termed muscular dystrophy-dystroglycanopathies (MDDG). A new nomenclature based on clinical severity and genetic cause was recently proposed by OMIM. The severity classifications are A (severe), B (intermediate), and C (mild). The subtypes are numbered one to six according to the genetic cause, in the following order: (1) POMT1, (2) POMT2, (3) POMGNT1, (4) FKTN, (5) FKRP, and (6) LARGE.

Most common severe types include:

Nodular sclerosis (or "NSHL") is a form of Hodgkin's lymphoma that is the most common subtype of HL in developed countries. It affects females slightly more than males and has a median age of onset at ~28 years. It is composed of large tumor nodules with lacunar Reed–Sternberg cell (RS cells) surrounded by fibrotic collagen bands.

The British National Lymphoma Investigation further categorized NSHL based upon Reed-Sternberg cells into "nodular sclerosis type I" (NS I) and "nodular sclerosis type II" (NS II), with the first subtype responding better to treatment.

This disorder causes neurological problems, including mental retardation, brain atrophy and ventricular dilation, myoclonus, hypotonia, and epilepsy.

It is also associated with growth retardation, megaloblastic anemia, pectus excavatum, scoliosis, vomiting, diarrhea, and hepatosplenomegaly.

An "Addisonian crisis" or "adrenal crisis" is a constellation of symptoms that indicates severe adrenal insufficiency. This may be the result of either previously undiagnosed Addison's disease, a disease process suddenly affecting adrenal function (such as adrenal hemorrhage), or an intercurrent problem (e.g., infection, trauma) in someone known to have Addison's disease. It is a medical emergency and potentially life-threatening situation requiring immediate emergency treatment.

Characteristic symptoms are:

- Sudden penetrating pain in the legs, lower back, or abdomen

- Severe vomiting and diarrhea, resulting in dehydration

- Low blood pressure

- Syncope (loss of consciousness and ability to stand)

- Hypoglycemia (reduced level of blood glucose)

- Confusion, psychosis, slurred speech

- Severe lethargy

- Hyponatremia (low sodium level in the blood)

- Hyperkalemia (elevated potassium level in the blood)

- Hypercalcemia (elevated calcium level in the blood)

- Convulsions

- Fever

The symptoms of Addison's disease develop gradually and may become established before they are recognized. They can be nonspecific and are potentially attributable to other medical conditions.

The signs and symptoms include fatigue; lightheadedness upon standing or difficulty standing, muscle weakness, fever, weight loss, anxiety, nausea, vomiting, diarrhea, headache, sweating, changes in mood or personality, and joint and muscle pains. Some patients have cravings for salt or salty foods due to the loss of sodium through their urine. Hyperpigmentation of the skin may be seen, particularly when the patient lives in a sunny area, as well as darkening of the palmar crease, sites of friction, recent scars, the vermilion border of the lips, and genital skin. These skin changes are not encountered in secondary and tertiary hypoadrenalism.

On physical examination, these clinical signs may be noticed:

- Low blood pressure with or without orthostatic hypotension (blood pressure that decreases with standing)

- Darkening (hyperpigmentation) of the skin, including areas not exposed to the sun. Characteristic sites of darkening are skin creases (e.g., of the hands), nipple, and the inside of the cheek (buccal mucosa); also, old scars may darken. This occurs because melanocyte-stimulating hormone (MSH) and ACTH share the same precursor molecule, pro-opiomelanocortin (POMC). After production in the anterior pituitary gland, POMC gets cleaved into gamma-MSH, ACTH, and beta-lipotropin. The subunit ACTH undergoes further cleavage to produce alpha-MSH, the most important MSH for skin pigmentation. In secondary and tertiary forms of adrenal insufficiency, skin darkening does not occur, as ACTH is not overproduced.

Addison's disease is associated with the development of other autoimmune diseases, such as type I diabetes, thyroid disease (Hashimoto's thyroiditis), celiac disease, or vitiligo. Addison’s disease may be the only manifestation of undiagnosed celiac disease. Both diseases share the same genetic risk factors (HLA-DQ2 and HLA-DQ8 haplotypes).

The presence of Addison's in addition to mucocutaneous candidiasis, hypoparathyroidism, or both, is called autoimmune polyendocrine syndrome type 1. The presence of Addison's in addition to autoimmune thyroid disease, type 1 diabetes, or both, is called autoimmune polyendocrine syndrome type 2.