Hereditary Angioedema

Hereditary angioedema (HAE) is a rare, genetic condition that causes episodes of swelling in different parts of your child’s body, including their face, hands or feet. Sometimes, swelling can happen in areas you can’t see, like in the tissues that line your child’s airways or digestive organs.

This swelling occurs because fluid leaks out of tiny blood vessels in your child’s body. The fluid builds up in the nearby tissues, which can prevent blood or lymph from moving along as it should. Episodes of swelling and related symptoms (HAE attacks) can be unpredictable and range in severity from mild to life-threatening.

“Angio-” refers to blood vessels, and “-edema” is the medical term for swelling due to fluid buildup within bodily tissues. There are many types of angioedema, each with different causes. HAE is one of the rarer types. It’s congenital, which means a person is born with it.

If your child has been diagnosed with HAE, you might feel uncertain of what comes next. It may help to know that research continues to provide new treatments for people of all ages with HAE — including children. Your child’s care team can help you learn which treatments are suitable for them and what you can expect down the road.

Types of hereditary angioedema

HAE is one type of angioedema, but healthcare providers also divide HAE into different types:

• Type I HAE. This is the most common type, responsible for about 85% of all HAE cases. It’s when your child’s body doesn’t make enough of a certain protein called C1-Inhibitor (C1-INH). Without enough C1-INH, inflammation and related swelling can occur in your child’s body. Providers also call this type C1-INH deficiency.
• Type II HAE. This is the next most common type. Your child’s body can make enough C1-INH, but the protein doesn’t function as it should.
• HAE with normal C1-INH. This type is the least common. Your child has normal levels of C1-INH, and the protein functions normally. However, other factors cause swelling to happen.

Taken together, types I and II HAE affect 1 in every 50,000 people. This means about 6,000 people in the U.S. have one of these types of HAE. Researchers don’t know how many people have HAE with normal C1-INH, but they know it’s very rare.

Symptoms of hereditary angioedema

HAE signs and symptoms vary from person to person and may include:

• Visible swelling in various parts of your child’s body, including their hands, feet, eyelids, lips and genitals
• Symptoms related to swelling in your child’s gastrointestinal (GI) tract, which include nausea, vomiting, diarrhea and abdominal pain
• Symptoms related to swelling in your child’s mouth, throat and airways — including difficulty swallowing, swelling of your child’s tongue, a gasping sound when your child inhales and a change in how their voice sounds

Call 911 or your local emergency number immediately if your child struggles to breathe or swallow. Swelling affecting the airways is a life-threatening complication of HAE that can be fatal without treatment.

HAE doesn’t cause hives. This makes HAE different from other forms of angioedema, like acute allergic angioedema. However, some people with HAE develop a non-itchy rash as an early warning sign before swelling develops.

HAE attacks typically last three to five days. The attacks come and go and can be hard to predict.

When do HAE symptoms begin?

HAE symptoms usually begin during childhood or adolescence and often worsen at puberty. They may start as early as age 2. About 50% of people with type I or type II HAE develop symptoms by age 10. Attacks may happen more often and with greater severity after puberty. Nearly everyone with type I or type II HAE shows symptoms by age 20.

People who have HAE with normal C1-INH start to show symptoms a bit later in life — usually in their late teens or early adulthood.

What are the triggers for HAE attacks?

It’s not always clear what triggers an HAE attack. Some known triggers include:

• Physical injury or minor trauma
• Dental procedures
• Surgery
• Anxiety or emotional stress
• Viral infections, like a cold or flu
• Certain physical activities, like typing, hammering or shoveling

You may not be able to tell what triggers an attack in your child. But it may help to keep a journal of when the attacks happen and what’s going on at the time (for example, if your child is sick or dealing with a stressful situation).

Hereditary angioedema causes

A mutation (change) to the SERPING1 gene causes both type I and type II HAE. This gene tells your child’s body how to create the C1-INH protein. If your child has type I HAE, that means the mutation prevents their body from making enough C1-INH. If your child has type II HAE, their body can produce enough C1-INH, but the mutation prevents the protein from functioning normally.

Researchers continue to explore the causes of HAE with normal C1-INH. They know mutations to the following genes can cause it:

• F12
• ANGPT1
• PLG
• KNG1

In some cases, people have HAE without an identifiable gene mutation. Healthcare providers call this HAE-unknown.

The genetic mutations that cause HAE prevent certain proteins in your child’s body from working as they should. These proteins help fluids flow normally through your child’s tiny blood vessels, known as capillaries. But when these proteins aren’t working right, fluid leaks and builds up in the tissues surrounding your child’s blood vessels, leading to HAE symptoms.

Hereditary angioedema inheritance

HAE occurs through an autosomal dominant pattern of inheritance. This means just one copy of an abnormal gene is enough to cause the condition. A child can inherit this abnormal gene from either parent.

Most people with HAE have a family history of the condition. But sometimes, a genetic mutation can spontaneously occur (de novo or “new”). This means a mutation happens for the first time in a person without a known family history.

How doctors diagnose this condition

If your child has signs or symptoms of HAE, a provider will:

• Do a physical exam
• Talk to you about your child’s symptoms and their medical history
• Do blood tests to check their C1-INH levels and function
• In some cases, do genetic testing to look for the mutations that cause HAE

How is hereditary angioedema treated?

There are two main categories of medications available for people with HAE:

• On-demand medications, like Berinert® or Kalbitor®. These treat an HAE attack right when it happens. Taking these medications as soon as possible after symptoms begin can reduce an attack’s severity and prevent life-threatening complications.
• Prophylactics (preventive medications), like Cinryze®, Haegarda® or Takhzyro®. These medications lower the risk of an attack happening. Your child’s provider may prescribe a prophylactic medication in the context of a known trigger (like a dental procedure). Or they may prescribe it long-term, depending on your child’s needs.

Experts agree that on-demand medications are crucial and potentially lifesaving. Your child needs these medications on hand at all times and in all settings (like home and school), even if they’re also taking prophylactic medications.

Your child’s provider will tell you exactly which medications your child needs, how they should receive them and when. They’ll also explain which medications your child is eligible to take according to their age. Be sure to follow their instructions closely and ask if anything is unclear.

How soon after treatment will my child feel better?

On-demand medication to help treat an HAE attack will help your child feel better relatively quickly. Once they begin treatment, their symptoms should improve within 30 minutes to two hours. Your child’s provider can tell you more about what to expect and how to manage at-home treatment.

How do I take care of my child if they have HAE?

Seeing your child experience an HAE attack may make you feel helpless. But there’s a lot you can do to take care of your child before, during and after an attack:

• Keep on-demand medications available. These can be lifesaving. Make sure you can recognize when your child needs the medications. Also, be sure you know how to administer them. Your provider will tell you more.
• Don’t treat an HAE attack as an allergy. Medications like antihistamines and epinephrine — commonly used for allergies — won’t help an HAE attack. So, don’t give these medications to your child.
• Be aware of what triggers an attack. Triggers can vary from person to person. Keep a list of triggers that cause your child to have an attack and share these with their healthcare provider. Try to help your child avoid these triggers. When they’re unavoidable, ask your provider if prophylactic medications are appropriate.

When should I seek care for my child?

Call a healthcare provider if:

• You believe your child has symptoms of hereditary angioedema
• Your child has new or changing symptoms associated with an HAE attack
• Your child’s medications aren’t working as expected

When should I go to the emergency room?

Seek emergency care if your child experiences:

• Trouble swallowing
• Trouble breathing
• Any signs of tongue or throat swelling (even if they’ve taken medication at the first signs of an attack)

These could be signs of dangerous swelling that’s affecting your child’s airways. Don’t delay seeking care. This swelling can be life-threatening.

What questions should I ask my child’s healthcare provider?

You may wish to ask:

• What type of HAE does my child have?
• Which treatments do you recommend?
• How do I know when my child needs on-demand medication?
• Does my child need preventive medication, and if so, when?
• Are there any activities or situations my child should avoid?
• What’s the outlook for my child?

Can HAE be prevented?

There’s no known way to prevent HAE. If you or your partner has HAE and are considering having a child, you may wish to speak with a genetic counselor. They can help you understand the chances of passing the condition on to your child.

What can I expect if my child has HAE?

HAE is a lifelong condition. But treatment can help lessen the impact of the condition on your child’s life. It can also lower the risk of life-threatening symptoms, like swelling of your child’s airways.