Autoimmune polyendocrine syndrome type 1

Overview

Autoimmune Polyendocrine Syndrome Type 1 (APS-1), also known as Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED), is a rare, inherited autoimmune disorder. It is characterized by the dysfunction of multiple endocrine glands due to autoimmune destruction, alongside non-endocrine manifestations such as chronic mucocutaneous candidiasis (fungal infections) and ectodermal abnormalities.

APS-1 typically begins in childhood and follows a chronic, progressive course. It is distinguished from other types of autoimmune polyendocrine syndromes by its genetic basis and unique triad of symptoms.

Causes

APS-1 is caused by mutations in the AIRE (Autoimmune Regulator) gene, located on chromosome 21. The AIRE protein is crucial for immune system tolerance—training the body to recognize self-tissues and prevent autoimmune attacks.

The condition follows an autosomal recessive inheritance pattern, meaning a person must inherit two mutated copies of the AIRE gene (one from each parent) to develop the disease. Carriers (with one mutation) usually do not show symptoms.

Symptoms

APS-1 is defined by a clinical triad of:

1. Chronic mucocutaneous candidiasis (CMC) – persistent fungal infections of the skin, nails, and mucous membranes

2. Hypoparathyroidism – leading to low calcium levels, causing muscle cramps or seizures

3. Primary adrenal insufficiency (Addison’s disease) – causing fatigue, low blood pressure, and electrolyte imbalances

Other possible features include:

• Delayed puberty or premature ovarian/testicular failure

• Autoimmune hepatitis

• Type 1 diabetes mellitus

• Alopecia (hair loss)

• Vitiligo (loss of skin pigment)

• Chronic diarrhea or malabsorption

• Pernicious anemia

• Autoimmune thyroiditis

• Dental enamel hypoplasia

Not every individual will have all symptoms. The condition is variable, and new autoimmune conditions may develop over time.

Diagnosis

Diagnosis of APS-1 is based on clinical findings, family history, and genetic testing.

Diagnostic criteria include:

• Presence of at least two of the classic triad: CMC, hypoparathyroidism, and adrenal insufficiency

• Early onset of symptoms (typically in childhood or adolescence)

• Detection of AIRE gene mutations by genetic testing (confirmatory)

• Blood tests showing:

  • Low calcium, high phosphate (hypoparathyroidism)

  • Low cortisol, high ACTH (adrenal insufficiency)

  • Positive autoantibodies (e.g., anti-interferon antibodies)

Treatment

There is no cure for APS-1. Treatment focuses on managing individual autoimmune manifestations with hormone replacement, antifungal therapy, and immunosuppressive strategies.

Endocrine management:

• Calcium and vitamin D supplementation: For hypoparathyroidism

• Hydrocortisone or fludrocortisone: For adrenal insufficiency

• Insulin therapy: For type 1 diabetes

• Sex hormone replacement: In cases of gonadal failure

Other treatments:

• Antifungal medications: For chronic candidiasis (topical or systemic)

• Immunosuppressive drugs: Occasionally used to manage autoimmune hepatitis or severe complications

• Nutritional support: For patients with malabsorption or chronic diarrhea

Prognosis

The long-term outlook for individuals with APS-1 varies depending on the severity and number of organs affected. With early diagnosis and lifelong hormone replacement therapy, many individuals can lead stable lives. However, untreated adrenal crises or severe infections can be life-threatening.

Prognostic considerations include:

• Increased risk of life-threatening adrenal crisis

• Complications from infections (especially candidiasis)

• Progressive development of new autoimmune conditions over time

• Regular follow-up and organ monitoring are essential for early intervention

Genetic counseling is recommended for affected families to understand inheritance patterns and guide reproductive decisions.