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What

Polyglandular Autoimmune Syndrome, type 1 (PGA-1) is a very rare genetic autoimmune disorder characterized by skin infections with a specific type of fungus and decreased function of several endocrine glands. These endocrine glands make hormones that control the body’s metabolism and other body functions. There are three types of PGA; types 2 and 3 occur only in adults and are separated by the endocrine glands affected.

Who

PGA-1 is a very rare disorder. It occurs more frequently in Finnish, Iranian-Jew and Sardinian populations. In Finland, PGA-1 is estimated to occur in 1 in 25,000 children. Boys and girls are affected equally. PGA-1 is inherited in an autosomal recessive manner, meaning that two genes with a change are needed for this disease to occur, one changed gene inherited from each parent. The parents of the affected child are healthy because they have one normal gene, but each parent carries a copy of the changed gene which they have passed on to their child. When both parents are carriers of this gene change then there is a 25% chance that each pregnancy could be affected by this disorder. Parents usually do not know they are carriers and they have no control over which genes get passed on. Also, spontaneous mutations in the gene can occur and are responsible for PGA-1 in some cases.

Signs and Symptoms

Manifestations of PGA-1 occurs in children between 3 to 5 years of age. The first and most common symptom is candidiasis, infection with a type of fungi named Candida albicans. This starts before the age of 5 years and occurs in almost all children with PGA-1. Children with PGA-1 have difficulty fighting off candida and have recurrent infections of the skin, nails, vagina, mouth, and anus. The fungus may infect the esophagus as well; however, it rarely enters the blood. The first endocrine gland to be affected is the parathyroid gland and decreased production of parathyroid hormone leads to a condition called hypoparathyroidism. The parathyroid gland is important in controlling calcium levels in the blood. When parathyroid hormone levels are low, calcium levels drop. The child will experience hand and leg muscle cramps and numbness, and tingling of the lips, fingers, and feet. If calcium levels drop too low, seizures and arrhythmia (irregular heart beat) can occur. The second endocrine gland to be involved is the adrenal gland. When the adrenal gland does not make enough of a hormone named cortisol, Addison’s disease develops. Addison’s disease results in weakness, decreased energy, poor appetite, nausea, vomiting, diarrhea, brownish coloring of the palms and soles, and increased sensitivity to cold climate. In severe cases, low blood sugar, weight loss, dehydration, dizziness, low blood pressure, and arrhythmia due to high blood potassium levels can develop. Children with PGA-1 can have other signs and symptoms including; underdeveloped tooth enamel, nail abnormalities, the ovaries and testes may be affected, hair loss, diabetes if the pancreas is attacked, hypothyroidism if the thyroid gland is impaired, hepatitis, inflammation of the eye, loss of skin pigment, and diarrhea.

Possible Causes

PGA-1 is caused by genetic changes (mutations) in a gene named AIRE located on chromosome 20. The AIRE gene makes a protein that regulates the immune system. The immune system normally makes antibodies to attack foreign invaders such as bacteria, viruses and fungi. When the AIRE gene is not working correctly, the body’s immune system is unable to fight off skin infections with fungi and makes antibodies to attack healthy cells of the body instead.

Diagnosis

The diagnosis of PGA-1 should be considered when a child has symptoms suggestive of more than one hormonal deficiency. Blood tests can identify the presence of antibodies directed against the adrenal cortex, thyroid gland, stomach cells, or pancreas. Not all patients will have all antibodies and some antibodies may develop later in life. Also, blood tests can detect decreased ovarian, testicular, thyroid gland, and adrenal cortex function.

Treatment

Antifungal medications are used to treat the candida infections and hormones are given to replace the missing natural hormones. In hypoparathyroidism, calcium and vitamin D supplementation combined with a diet rich in calcium is recommended. In Addison’s disease, steroids are needed to prevent a crisis during stress. If diabetes is present, insulin injections will be necessary.

Prognosis

The prognosis for patients with PGA-1 depends on how many and how severely different glands are affected. The earlier symptoms appear, the greater the likelihood that multiple glands will be affected. Close follow-up with an endocrinologist is important for monitoring the progress of this disease.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.

Weblinks

Brain talk Communities
Online patient support groups.

Genetic Information and Patient Services, Inc (GAPS)
Provides workshops and seminars for parents of children who have autoimmune diseases.

Google Search for Polyglandular Autoimmune Syndrome, Type 1

References and Sources

www.emedicine.com/med/topic1869.htm www.medterms.com/script/main/art.asp?articlekey=14344 www.medical-library.net/sites/framer.html?/sites/_polyglandular_syndromes.html