Autoimmune Polyglandular Syndrome Type 1

What is autoimmune polyglandular syndrome type 1 (APS1)?

Autoimmune polyglandular syndromes (APSs), also called autoimmune polyendocrine syndromes, are a group of rare diseases that all involve autoimmune activity against multiple endocrine organs (like the hypothalamus, thyroid, pancreas, reproductive glands, pituitary gland, adrenal glands, pineal body, etc.). In autoimmune diseases, for unknown reasons the body attacks and damages its own tissues. Autoimmune polyglandular syndrome type 1 (APS1), also known as APECED Syndrome, is an inherited collection of diseases that affects many organs in the body. It has several characteristic symptoms that usually begin in childhood or adolescence. APS1 is a very rare disorder; in the United States, it affects about 1 in every 2 to 3 million births. To read about autoimmune polyglandular syndrome type 2 and type 3, click here and here, respectively.

What are the symptoms of autoimmune polyglandular syndrome type 1?

The symptoms in each person with this condition can be variable. However, every patient will have components of at least two of the three major conditions that appear in this syndrome:

Chronic mucocutaneous candidiasis: Persistent and recurring yeast infections of the skin, nails, oral cavity (called thrush), and/or mucous membranes. Oral cavity infections and esophageal infections are common. Nails may be abnormally thick, discolored, and swollen. Vaginal infections occur frequently in women.
Hypoparathyroidism: The parathyroid glands in the neck do not function at the level they should be. This leads to low levels of calcium and high levels of phosphorus in the blood. This can cause muscle cramps and spasms, rigidity, headaches, excessive nervousness, and seizures.
Adrenocortical insufficiency (Addison’s disease): The adrenal glands (located above the kidneys) do not produce enough hormones. Without enough of those hormones, symptoms may appear, including low blood pressure, muscle cramps, weakness, faintness, diarrhea, nausea, vomiting, dehydration, changes in skin color, and a small heart.

Other symptoms may include the following:

Type 1 diabetes
Autoimmune liver disease
Ovarian failure
Gastro-intestinal cancers and cancers of the tongue
Early onset pernicious anemia from atrophic gastritis

What causes autoimmune polyglandular syndrome type 1?

Human traits are inherited from one’s father and mother. They each contribute a gene, which interacts with the other. APS1 is inherited in an autosomal recessive pattern, which means that both parents need to pass down a copy of the defective gene for the condition to occur. APS1 is caused by mutations of the gene called the AIRE gene. This AIRE gene carries instructions on creating a protein called the autoimmune regulator, which appears in the thymus gland. If there is a deficiency of this protein, then certain T-cells that the thymus gland creates can escape into the circulation, instead of being destroyed in the thymus like they’re supposed to be. This results in the autoimmune activity.

How is autoimmune polyglandular syndrome type 1 diagnosed?

APS1 is diagnosed using the following procedures:

Blood tests that analyze the DNA; specifically, mutations in the AIRE gene
Diagnoses of at least two of the three major disease components (Chronic mucocutaneous candidiasis, Hypoparathyroidism, and Adrenocortical insufficiency/Addison’s disease)
Recording of patient history
Thorough physical examination

What are the treatments for autoimmune polyglandular syndrome type 1?

APS1 treatment currently targets the specific component diseases that appear in each patient. These treatments include, but are not limited to:

Replacement therapy of lacking endocrine hormones
Educating patients about the signs and symptoms of component diseases
Hormone replacement therapy, either via oral medications or injections, to treat Addison’s disease
Calcium and Vitamin D supplements to treat hypoparathyroidism
Oral fluconazole to treat chronic mucocutaneous candidiasis