autoimmune polyendocrine syndrome type 1

Autoimmune polyendocrine syndrome type 1 (APS1), also called APECED, is a multisystem autoimmune condition that usually begins in childhood or early adolescence. It is marked by the combination of chronic yeast infections of the skin and mucous membranes, low parathyroid hormone levels causing calcium imbalance, and autoimmune destruction of the adrenal glands. The underlying cause is a harmful change in the AIRE gene, a key regulator that teaches the immune system to recognize the body’s own tissues. APS1 affects males and females equally and is considered rare, occurring in roughly one to nine individuals per million people. Severity and symptoms vary widely between individuals.

The first feature that often brings APS1 to medical attention is chronic mucocutaneous candidiasis—persistent yeast infections of the mouth, skin, or nails that begin in early childhood. Endocrine problems typically follow. Many children develop hypoparathyroidism, which can cause tingling, muscle cramps, or episodes of hypocalcemic tetany, and later autoimmune adrenal insufficiency, which may present with fatigue, weight loss, low blood pressure, or salt craving. Over time, other glands can be affected, leading to premature ovarian insufficiency in some females, hypogonadism, or hypothyroidism. Beyond the endocrine system, APS1 can involve the eyes and skin. Pigmentary retinopathy and reduced visual acuity may limit peripheral vision, while nail dystrophy, enamel hypoplasia, and alopecia are reported in a subset of individuals. Recurrent fungal infections, pancreatitis, cholelithiasis, chronic diarrhea, and asplenia reflect broader immune dysregulation. Not all individuals experience all features, and the timing as well as the combination of manifestations can differ even among affected members of the same family.

APS1 results from pathogenic variants in the AIRE gene. The AIRE protein promotes immune tolerance by helping the thymus expose developing immune cells to a wide range of the body’s proteins. When AIRE does not function correctly, self-reactive immune cells escape deletion and can attack multiple organs. Most reported cases follow an autosomal recessive inheritance pattern, meaning a child must receive one altered AIRE copy from each parent to be affected. When both parents are carriers they are typically healthy but have a 25 percent chance with each pregnancy of having an affected child. This condition is more common when parents share a common ancestor, because the chance that both carry the same rare variant is higher in such families. Less commonly, single altered copies can act in an autosomal dominant manner, and in those families each child of an affected individual has a 50 percent chance of inheriting the variant. Even within one inheritance pattern, the specific symptoms and their severity can differ considerably, a phenomenon called variable expressivity. Genetic counseling is recommended for families to review testing options and recurrence risks.

At present, management focuses on treating each endocrine deficiency and controlling infections. Lifelong hormone replacement for hypoparathyroidism and adrenal insufficiency is standard, and antifungal medications are used to manage chronic candidiasis. Additional endocrine issues such as hypothyroidism or gonadal insufficiency are treated as they arise. Long-term care should be coordinated through a multidisciplinary team that may include endocrinologists, immunologists, dermatologists, and ophthalmologists. Regular surveillance is an essential part of care, with scheduled monitoring of adrenal function, calcium levels, eye health, dental integrity, and growth parameters helping to detect complications early. Because needs differ between individuals, treatment plans are personalized and should be reviewed periodically with specialists familiar with APS1.

With attentive hormone replacement, infection control, and routine monitoring, many people with APS1 live into adulthood and pursue typical activities. Outcomes depend on how many organs become involved, how early endocrine crises are recognized, and access to experienced specialists. Serious complications such as adrenal crisis, severe infections, or chronic organ damage can occur, but proactive management reduces these risks. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with expert centers and genetic counselors to stay informed about optimal management and emerging research.

Several clinical trials are currently investigating new ways to modulate the immune system or prevent organ damage in APS1. Areas of interest include immune-targeted therapies and novel antifungal approaches. Individuals interested in research participation can search ClinicalTrials.gov or discuss eligibility with their healthcare team.