Hereditary angioedema (HAE) is an uncommon but serious genetic disorder that causes swelling in different parts of the body.
Genetic variants may cause one of three types of HAE:
Type 1 occurs when blood levels of a protein called C1 inhibitor (C1-INH) are low.
Type 2 happens when C1-INH protein is not working properly.
Type 3 is very rare. C1-INH protein levels are normal, but HAE is due to other genetic changes.
All of the genetic changes that cause HAE ultimately affect how your body controls inflammation, and all can lead to severe swelling.
There’s no way to prevent or get rid of HAE if you carry one of the genetic variants that causes it, but you may be able to manage your symptoms by identifying possible triggers and taking prescribed medications.
HAE Causes: A Handful of Genetic Changes
HAE occurs as a result of a genetic change. The mechanism of an HAE attack varies depending on which genetic change you have.
There are known mutations in the SERPING1 gene and a few other genes. Scientists suspect there are also other as yet unidentified genes that cause HAE. Which genetic change you have may influence the type of treatment your doctor prescribes.
Changes in the SERPING1 Gene Cause HAE Type 1 and 2
Changes in the C1NH gene, also known as the SERPING1 gene, cause type 1 and type 2 HAE.
The SERPING1 gene tells the body how to make a protein called C1-INH, which is important for controlling swelling. In type 1 HAE, your body does not make enough C1-INH protein. With type 2, your body makes enough of the protein, but it doesn’t work properly.
Without normal and functional amounts of C1-INH protein, the body generates too much bradykinin, a protein peptide. Bradykinin causes excessive fluid to leak through the walls of blood vessels, which leads to inflammation and episodes of swelling.
Genetic Changes That Cause HAE With Normal C1-INH Levels
This type of HAE is an extremely rare form of the disease. Its exact prevalence isn’t known. Scientists believe changes in the F12 gene cause this type.
In this type of HAE, C1-INH protein levels and functioning are normal, but the F12 changes cause dysregulation in the bodily system that makes a protein called coagulation factor XII. This protein plays a role in stimulating inflammation and producing bradykinin.
Variants in several other genes are currently thought to be implicated in HAE with normal C1-INH protein levels. Other cases have no known causes and could be due to variants that haven’t yet been identified.
HAE: How Is It Passed Down?
HAE is usually inherited in an autosomal dominant pattern. That means that if you inherit one abnormal copy of the gene from only one parent, it’s enough to get the disease. If your mom or dad has HAE, you have a fifty-fifty chance of having it, too.
HAE can also develop in people with no family history of it if a spontaneous gene change happens when fetal cells are dividing in the uterus.
Testing for HAE
Tests can show whether a person has HAE. The simplest form of testing involves a blood test that measures levels of C1-INH protein or how well this protein works in your body. Sometimes, a blood test looks for other biomarkers of the disease, too.
Other testing includes monitoring C4 protein or D-dimer protein levels during acute attacks.
Genetic testing can be used as a follow-up test to confirm the results of the blood test, if necessary.
Testing for HAE is a personal choice, and it can be scary for some people. But knowing that you have the disease can help prepare you or your loved ones for future attacks, allowing you to take advantage of preventive treatments early and take control of your health.
What Are HAE Attack Triggers?
HAE attacks may involve severe swelling in the skin (typically of the face, limbs, genitals, or buttocks), gastrointestinal tract, or airway.
Certain factors may prompt an HAE attack. These include:
Stress Anxiety and stress can both be triggers.
Common Illnesses Having an injury or an infection, such as a cold or flu, may bring on an HAE episode.
Pregnancy, Menstruation, or Breastfeeding Many women report an increase in the number of attacks during their period or at other times when they experience hormonal changes.
Drugs Medications such as oral contraceptives and angiotensin-converting enzyme inhibitors are linked to an increase in the number and severity of HAE episodes.
Medical Procedures Some studies have shown that attacks after surgery are common. They typically happen 4 to 30 hours later. Having a dental procedure may also trigger an HAE episode.
Some people also report swelling after engaging in activities such as:
Typing or writing
Pushing a lawn mower
Shoveling
Hammering
Other physical activities
While it’s hard to predict when an HAE episode will happen, some people report symptoms that forecast a problem. These can occur several hours or even a full day before the attack.
Common symptoms of an impending HAE attack include:
Fatigue
Irritability
Weakness
Nausea
Rash
Avoiding HAE Triggers
It might be impossible to avoid all HAE triggers, but there are some steps you can take to lessen your chances of a severe attack.
Treatment for HAE includes preventive medications to protect against attacks as well as medications that can reduce the severity of symptoms once an attack has started.
Talk to your doctor before taking any new medications or having a procedure that could provoke a swelling episode. Short-term prophylaxis, in the form of intravenous plasma-derived C1-INH protein concentrate, can be given just before a surgical or dental procedure to prevent an HAE attack during or following the procedure.
Psychological stress is a common trigger of HAE attacks. The effects of a chronic medical condition on mental health can lead to a cycle in which depression, anxiety, and post-traumatic stress disorder (PTSD) develop as a result of HAE attacks and then trigger future attacks.
In addition to therapy and mental health support, other lifestyle strategies can help keep your stress levels low. These include:
Getting enough sleep
Exercising daily
Practicing meditation, deep breathing techniques, or yoga
Some people keep a journal of their HAE attacks. This can help you better identify triggers and potentially avoid them.
The Takeaway
Hereditary angioedema (HAE) is a genetic condition that causes repeated episodes of severe, painful swelling, typically in the face, hands, feet, and genitals but also in the airway or intestinal walls.
Genetic variants, which are either inherited or occur during gestation, may cause one of three types of HAE.
Triggers of HAE attacks can include stress, illnesses such as colds and flu, certain medications, and more.
One of the best ways to manage HAE is to be aware of triggers that may lead to an attack.
