Hereditary Angioedema (HAE) Type I

What is Hereditary Angioedema (HAE) Type I?

Hereditary Angioedema (HAE) Type I is a rare, inherited genetic disorder that causes recurrent episodes of severe swelling (angioedema) in various parts of the body. These episodes most commonly affect the face, lips, throat, abdomen, limbs, and genitals. Swelling can be painful, unpredictable, and, in some cases, life-threatening—especially when it involves the airways.

HAE affects approximately 1 in 50,000 people worldwide. Type I is the most common form, accounting for about 85% of all HAE cases. The disorder is inherited in an autosomal dominant manner, meaning a child has a 50% chance of inheriting the condition if one parent is affected.

What Causes HAE Type I?

HAE Type I is caused by a genetic mutation that leads to low levels of a protein called C1 esterase inhibitor (C1-INH). This protein helps regulate inflammation by controlling the complement system and the production of bradykinin—a chemical that increases blood vessel permeability and causes fluid to leak into surrounding tissues.

In people with HAE Type I:

The C1-INH antigen level is low
The C1-INH protein function is also reduced
Bradykinin builds up, leading to swelling

HAE is not caused by allergies and does not respond to antihistamines, corticosteroids, or epinephrine, making early and accurate diagnosis essential.

Key Symptoms of HAE Type I

Recurrent swelling in the face, hands, feet, arms, legs, or genitals
Abdominal pain, bloating, nausea, or vomiting due to swelling of the intestinal wall
Throat or airway swelling (laryngeal edema), which can be life-threatening
Episodes that may last 2 to 5 days
No itching or hives (distinguishing it from allergic angioedema)
Symptoms usually begin in childhood or adolescence and may worsen over time without treatment
Some patients experience warning signs (prodromal symptoms) such as tingling, fatigue, or a rash before an attack

Attacks can be triggered by trauma, stress, certain medications, infections, dental procedures, or hormonal changes, but sometimes occur without any clear trigger.

How is HAE Type I Diagnosed?

Diagnosis typically involves:

C1 Esterase Inhibitor Antigen Test (C1-INH Ag): Measures the amount of C1-INH protein in the blood
C1-INH Functional Assay: Checks if the C1-INH protein works properly
Complement C4 Levels: Often low during and between attacks
Genetic Testing: Can confirm the diagnosis, especially in patients with a family history of angioedema

How is HAE Type I Treated?

While there is no cure for HAE, several effective treatments are available to prevent or manage attacks:

Acute Attack Treatments

C1-INH concentrate (intravenous or subcutaneous)
Icatibant (a bradykinin receptor blocker, given by injection)
Ecallantide (a kallikrein inhibitor, given by injection)

Preventive Treatments (Prophylaxis)

Regular C1-INH replacement therapy
Lanadelumab (a kallikrein inhibitor injection)
Berotralstat (an oral kallikrein inhibitor)
Attenuated androgens (such as danazol) may be used in some cases, but are less common due to potential side effects

Additional Recommendations

Avoid known triggers when possible
Develop an emergency treatment plan, especially for airway swelling
Wear a medical alert bracelet
Ensure close contacts and healthcare providers are aware of the condition and emergency protocols

Why Early Diagnosis Matters

If left undiagnosed or misdiagnosed, HAE Type I can lead to delays in treatment, unnecessary surgeries (especially for abdominal symptoms), and potentially life-threatening laryngeal attacks. Early testing and proper treatment can significantly improve quality of life and reduce the risk of complications.

Bottom Line

Hereditary Angioedema Type I is a serious but manageable condition caused by a deficiency in C1 esterase inhibitor, leading to swelling that does not respond to standard allergy treatments. If you or a family member has unexplained, recurring swelling or abdominal pain—especially with a family history—talk to your doctor about testing for HAE. Early diagnosis and treatment are key to living well with this condition.