SNP Shot: Genomic Insights

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a genetic disorder affecting numerous organs throughout the body. It falls under the umbrella of autoimmune diseases, where the immune system mistakenly attacks the body's own healthy tissues and organs.

APECED symptoms typically emerge during childhood or adolescence. The condition is often characterized by a combination of three key features: chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and adrenal insufficiency. Individuals with APECED commonly exhibit at least two of these conditions, and many experience all three.

CMC involves persistent fungal infections caused by Candida, affecting the skin, nails, and mucous membranes lining body cavities. These recurring yeast infections can last for extended periods. CMC is usually the first symptom to appear in individuals with APECED, with almost all developing oral thrush. Esophageal infections are also frequent, while skin and nail infections occur less often. Vaginal yeast infections are common in women.

Other APECED symptoms arise from the immune system's attack on hormone-producing glands (the endocrine system). Hypoparathyroidism, a malfunction of the parathyroid glands, is another defining feature. These glands regulate calcium and phosphorus levels. Damage leads to reduced parathyroid hormone production (hypoparathyroidism). Symptoms include tingling in the lips, fingers, and toes; muscle pain and cramps; weakness; and fatigue. Severe hypoparathyroidism can cause life-threatening complications like voicebox spasms and seizures.

Adrenal insufficiency (autoimmune Addison disease), resulting from damage to the adrenal glands, is a third major characteristic of APECED. Reduced adrenal hormone production causes symptoms like fatigue, muscle weakness, loss of appetite, weight loss, low blood pressure, and skin discoloration. Other endocrine issues in APECED include type 1 diabetes (due to insufficient insulin), growth hormone deficiency (leading to short stature), reproductive organ problems (causing infertility), and thyroid dysfunction (resulting in various symptoms like weight gain and fatigue).

Autoimmune problems affecting non-endocrine tissues can lead to diverse additional symptoms in APECED. These are more common in North American populations compared to European populations. Hives-like rashes (urticarial eruptions) are frequent, often appearing in infancy or early childhood. Early symptoms may also include thin tooth enamel (enamel hypoplasia) and chronic diarrhea or constipation due to nutrient absorption problems. Additional APECED features, which can cause permanent organ damage if untreated, include stomach irritation (gastritis), liver inflammation (hepatitis), lung irritation (pneumonitis), dry mouth and eyes (Sjogren-like syndrome), eye inflammation (keratitis), kidney problems (nephritis), vitamin B12 deficiency, hair loss (alopecia), patchy loss of skin color (vitiligo), high blood pressure (hypertension), or a small/absent spleen (asplenia).

Inheritance:

APECED follows an autosomal recessive inheritance pattern, meaning both copies of the relevant gene must be mutated for the condition to manifest. Parents of an affected individual each carry one mutated gene copy but usually show no APECED symptoms. In rare instances, individuals with one copy of certain AIRE gene mutations may exhibit some APECED features, like CMC, hypoparathyroidism, or vitamin B12 deficiency, without the full range of symptoms. These individuals typically have one affected parent.