What is autoimmune polyendocrine syndrome?

Autoimmune polyendocrine syndrome is a rare, inherited disease in which the immune system mistakenly attacks many of the body’s tissues and organs. The mucous membranes and adrenal and parathyroid glands are commonly affected, though other tissues and organs may become involved as well.

The disease prevents the damaged glands from producing the hormones needed to adequately regulate some body functions. This can create a life-threatening condition if allowed to progress untreated.

Some signs of autoimmune polyendocrine disorder may appear in infancy and others may not show up until adolescence. The syndrome is slightly more likely to affect girls and is mostly limited to certain ethnic groups. These include Fins, Sardinians, and Iranian Jews. Less frequent clustering has been reported from northern Italy, northern Britain, Norway and Germany. Only about 500 cases of autoimmune polyendocrine disorder have been reported worldwide.

Signs and symptoms

The symptoms of autoimmune polyendocrine syndrome vary depending on which glands are affected. Children with this disorder have at least two of the following conditions and many have all three. The conditions occur in chronological order throughout the first decade and a half of childhood:

• Chronic mucocutaneous candidiasis (CMC) is a stubborn, recurring fungal infection of the skin, nails and mucous membranes. It appears by age 5. CMC appears in infants as diaper rash and thrush. Symptoms may include white patches on the tongue and inside of the mouth and a painful rash in the genital area.
• Hypoparathyroidism, a malfunction of the parathyroid glands, appears before age 10. The body is unable to make enough parathyroid hormone (PTH), which regulates calcium and phosphorous levels in the blood. Symptoms of this condition may include tingling in the fingertips, toes and lips; and muscle aches and fatigue.
• Adrenocortical insufficiency, also called Addison’s disease, is a condition in which the adrenal glands are unable to produce enough of the hormones cortisol and aldosterone. It appears before age 15. Symptoms may include weakness, muscle cramps, faintness, diarrhea, nausea and vomiting, low blood pressure and dehydration.

Other complications that occur less often include Type 1 diabetes, hepatitis, ovarian failure, alopecia and gastro-intestinal problems. These may arise until at least the fifth decade of life.  

Cause

Autoimmune polyendocrine syndrome is caused by defects in the autoimmune regulator (AIRE) gene. This gene plays a critical role in the body’s ability to distinguish between its own proteins and cells and those of bacteria and viruses. As a result, the body attacks its own healthy tissue. It is not well understood why defects in the AIRE gene affect only certain hormone-producing glands.

Autoimmune polyendocrine syndrome is an autosomal recessive genetic disorder. That means both parents must have a mutation of the AIRE gene for a child to be born with the disorder.

Parents who each have a single copy of the abnormal gene typically are not affected by the disease and likely don’t know they carry the mutation. There is a 25 percent chance that both will pass along the defective gene at conception and their child will be born with the disorder.

Testing and diagnosis

Your child’s doctor may order DNA testing for the AIRE mutation if your child has at least two of the three typical disease components (CMC, hypoparathyroidism and Addison’s disease). A blood test is used for DNA testing. Blood tests are also used to test for hypoparathyroidism and Addison’s disease. CMC is diagnosed through physical examination and a culture of the lesions.

Your child’s doctor may recommend testing organ and gland functions annually because new symptoms may appear throughout life. 

Treatment

Autoimmune polyendocrine syndrome is a lifelong condition that may involve more organs over time. Your child’s treatment will be targeted to the associated disorders and may include hormone replacement therapy and anti-fungal medications. You and your child will be taught to identify symptoms and signs of the syndrome to ensure immediate treatment and ongoing management of the condition.