Cause of Rare Disease That Affects This Country’s Residents Discovered

A rare autoimmune condition with a difficult name may affect people of Puerto Rican descent through a newly discovered genetic pathway, a finding that could eventually guide genetic counseling and treatment, scientists say.

The disorder is called autoimmune endocrinopathy-candidiasis-ectodermal atrophy, but doctors simply refer to the condition by its acronym, APECED. Affected people experience severe autoimmune attacks against their endocrine glands, but the disorder leaves no healthy tissue or organs.

Patients are particularly vulnerable to infections, caused by different species of Candida, the most common cause of fungal infections worldwide.

Most common symptoms

Among the symptoms of the disorder are skin rashes; alopecia; alternating bouts of chronic diarrhea and constipation; kidney problems; Addison’s disease, which affects the adrenal glands; damaged tooth enamel; and high blood pressure.

Dry eyes are also common among people with the disorder, according to Medical Express.

In advanced stages, APECED can be exacerbated by kidney failure, sepsis, and squamous cell carcinomas of the mouth and esophagus.

Overall, the disorder is considered very rare, with an estimated 1 in 100,000 to half a million people at risk.

Ethnic groups at risk

Ethnic groups at significant risk for APECED include Finnish Jews, Sardinians, and Iranians.

For these groups, an estimated 1 in 9,000 to 25,000 people are at risk.

Overall, APECED is not only rare, it is potentially fatal and occurs in most people with it through what are called bi-allelic mutations.

This means that the mutations are present in each allele — two copies — of a gene called AIRE. Each parent contributes one copy.

Discovering the Disease

In a study of 104 patients, researchers at the Laboratory of Clinical Immunology and Microbiology at the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, identified a small subset of these patients (17) with a newly identified gene sequence that causes the disease. Of these 17 patients, 15 were of Puerto Rican descent.

Dr. Sebastian Ochoa and his team confirmed that the AIRE gene is the sole cause of the autoimmune disorder. No other gene is mutated to cause APECED, but Ochoa and the NIAID team identified a new mutation that causes the condition.

The AIRE gene gets its name from its role: the autoimmune regulator gene—AIRE—which is at the heart of a series of harmful events. The most insidious of these events is the proliferation of a highly reactive population of T cells.

Among the 17 members of the study subset, Ochoa and his colleagues identified a faulty AIRE gene in relation to a newly identified genetic variant.

The team also found, in laboratory research, that this form of APECED may be reversible, a finding that paves the way for more intensive study and, potentially, an effective treatment.

Because of the Puerto Rican patient group in the study, Ochoa and colleagues say their research opens a new window into understanding the underlying genetics of APECED in this ethnic group.

In fact, the high incidence of the newly discovered AIRE variant among Puerto Ricans suggests that it may be a founder variant, brought to the island from the Cadiz region of Spain.