A Parent’s Guide to Hereditary Angioedema

Hereditary angioedema (HAE) is a rare genetic disorder that affects the immune system. It causes attacks of severe swelling in the skin, hands, feet, face, and airways. These attacks usually begin in childhood but tend to worsen after puberty.

HAE is a lifelong genetic condition that affects approximately one in 50,000 to 150,000 individuals worldwide. In the United States, it is thought that the disorder affects one in 50,000 people. Although these figures are estimated, the true prevalence of HAE remains unknown.

The severity of HAE varies significantly from person to person, and there are several types of the condition. This article will inform parents about the condition, including types, inheritance, symptoms, triggers, treatment, and supporting a child with HAE.

Types of HAE

People with HAE have a genetic defect in a protein called a C1 inhibitor. C1 inhibitor is found in the blood and works with the body’s immune system to balance the chemicals used to fight illness and respond to injuries. 

If there is not enough C1 inhibitor, or if it is defective, it can lead to the chemicals becoming imbalanced. This causes excess fluids to be released into body tissue, creating swelling. Swelling caused by excess fluid trapped in your body’s tissues is known as edema.

There are three types of HAE:

• Type I: People with type I HAE have low levels of the C1 inhibitor protein. 
• Type II: People with this type have normal levels of the C1 inhibitor protein, but it does not work correctly. 
• HAE with normal C1 inhibitor: In this type, C1 inhibitor protein levels are normal and it functions correctly. However, defects in three genes that control the production of factor XII and plasminogen (involved in clotting) and angiopoietin-1 (involved with blood vessel development) cause HAE in these individuals.

HAE type I is the most common form of this genetic condition. It accounts for 85% of cases.

Causes of HAE

Inheritance of HAE is autosomal dominant. This means that the genetic condition occurs when a child inherits one copy of a defective gene from one parent. For example, if a child has one parent with the defective gene, that child has a 50% chance of inheriting that defective gene.

Occasionally, HAE can occur in children whose parents do not have HAE or a defective gene. In these children, a spontaneous mutation of the gene occurs, causing HAE. The US Hereditary Angioedema Association discusses that up to 25% of HAE diagnoses result from a random mutation of the C1 Inhibitor gene.

Genetic Counseling

A genetic counselor can give you information about how a genetic condition can affect your family. They can discuss a wide range of topics with you, including:

• How HAE is passed from parent to child
• The potential benefits and disadvantages of genetic testing 
• Whether a genetic test is right for you 
• Types of genetic testing for HAE
• Advice on how to talk to your child, other family members, and friends about a genetic condition
• Managing your health through pregnancy if you have HAE

If you are not sure how to find a genetic counselor, speak to your family physician for guidance. You can also search for a genetic counselor on the National Society of Genetic Counselors directory.

Signs and Symptoms

Symptoms usually begin in childhood, get worse through puberty, and persist through adulthood. Fifty percent of people report that they experienced their first symptoms by the age of 7.

The main symptom of HAE is swelling due to a buildup of excess fluid (edema). The areas of the body most commonly affected are the hands, feet, eyelids, lips, genitals, and the mucous membranes that line the respiratory and digestive tracts.

A rash or itching does not accompany the swelling as it would in an allergic reaction. Instead, it tends to be hard and painful. Symptoms seen in different parts of the body include:

• Skin swelling (cutaneous edema): This usually occurs in the face, hands, arms, legs, genitals, and buttocks. It may be painful and unsightly but is temporary. Symptoms typically resolve in two to four days for most attacks.
• Abdominal symptoms (swelling of the membranes that line the gastrointestinal tract): These can cause abdominal pain, nausea, vomiting, and diarrhea.
• Upper airway membrane swelling: This can include the larynx (windpipe) and tongue and therefore be life-threatening. Swelling in these areas can cause upper airway obstruction, difficulty speaking, swallowing problems, and difficulty breathing.

The severity of attacks varies considerably, even within affected families. Less common symptoms have been identified, including neurological, pulmonary (lung), renal (kidney), urinary, and musculoskeletal symptoms.

Potential Triggers

Although symptoms can happen spontaneously, potential triggers have been identified. The most common triggers include:

• Anxiety
• Stress
• Minor trauma
• Surgery
• Colds, flu, and other viral infections
• Infected teeth and dental treatments
• Helicobacter pylori (a bacteria that can be present in the stomach)
• Intubation for anesthetics during an operation
• Hormone changes (especially puberty) 

Some people have also reported that symptoms are triggered following prolonged activities such as typing, lengthy periods of writing, shoveling, and hammering.

Treatment

Several options are available for both the treatment and prevention of HAE attacks, all approved by the Food and Drug Administration (FDA):

• Cinryze (C1 esterase inhibitor): This is approved for routine preventative treatment against HAE angioedema attacks in adults, adolescents, and pediatric patients (6 years old and above).
• Berinert (C1 esterase inhibitor—human):  This drug is used to treat acute HAE attacks in both adults and children. Berinert is delivered intravenously (in the vein), but it is designed to be self-administered after receiving training. 
• Ruconest (C1 esterase inhibitor—recombinant): This is approved to treat acute HAE attacks in adults and adolescents.
• Haegarda (C1 esterase inhibitor—human, pasteurized): This drug is prescribed for routine prevention of HAE attacks in patients 6 years and older.
• Orladeyo (berotralstat): This is used for routine prevention of HAE attacks in adults and pediatric patients 12 years and older. This medication is taken orally.
• Takhzyro (lanadelumab): This medication is approved to prevent HAE attacks in patients 12 years and older.
• Kalbitor (ecallantide): This is a treatment for acute attacks of HAE in patients older than 12 years and must be administered by a healthcare professional.
• Firazyr (icatibant generic): This drug can be used to treat acute attacks of HAE in adults over 18 years.

How to Support Your Child With HAE

Learning to cope with HAE is hard for children and teens. They experience physical symptoms such as pain and discomfort, along with the accompanying emotions such as fear, sadness, and anxiety. Talking to your child is the first step to supporting those living with HAE. 

By talking with your child, you can help them learn coping strategies and prepare them for an episode of symptoms. If you or your partner has HAE, share your experiences with your child so they won’t feel as worried and afraid if they witness you having an HAE attack.

There are supporting organizations that can help you and your child, such as the US Hereditary Angioedema Association. They offer advice and tool kits to support parents with children of all ages. Information is also available to help you discuss HAE with your child’s teachers, school nurse, and other people in their life. 

Encourage your child to ask you questions about HAE. If you are worried about not having the answers, you can seek help from your healthcare provider to get answers.

It’s also important to encourage your child to speak out and tell an adult if they are having symptoms, regardless of the setting, especially any symptoms in the throat, which can be dangerous.

Reassure your child that there are treatments to help them live life to the fullest. Explain that HAE should not stop them from pursuing and achieving their dreams. There is a range of treatments to help both prevent and treat HAE attacks. 

Raising a child with a genetic condition can be challenging for any parent. As well as supporting your child, make sure you get help too if you need it. Reach out to your healthcare provider, peers, or a support group if you feel stressed, anxious, worried, or depressed. Talking to families who also live with HAE can be a very beneficial way to cope.

Summary

Hereditary angioedema is a rare genetic disorder that produces attacks of severe swelling. It can be inherited or result from a new mutation in an individual. Swelling affecting the airway can be life-threatening.

Medications to manage the condition include those that can be given in case of a severe attack, as well as those that are given to prevent attacks. Parents can discuss the condition with their child and encourage them to report any symptoms immediately.

A Word From Verywell

Before 2008, treatment options were limited for HAE, but now there are several effective treatments to help manage the condition. You can also administer many medicines at home after instruction from a healthcare professional. With treatments continuously developing, it is becoming easier to manage life with HAE.