What Causes Hereditary Angioedema (HAE)?

Hereditary angioedema (HAE) is caused by a genetic defect that is inherited or developed at conception. These genetic changes may cause one of three types of HAE: HAE type 1, HAE type 2, or HAE type 3.e60dc2a1-f33c-4a05-9b50-8e3e8e5976299d584dbd-970a-4af7-850b-14398207fac3 The key to what goes wrong in hereditary angioedema is in the name of the disorder. The term “angio” is derived from the Greek word for “vessel,” in this case referring to blood vessels, and the word “edema” means “swelling.”e60dc2a1-f33c-4a05-9b50-8e3e8e59762904dd8e9e-df51-4420-887d-ac58af76d5de All of the genetic changes that cause HAE ultimately affect how your body controls inflammation, and all can lead to severe swelling.e60dc2a1-f33c-4a05-9b50-8e3e8e5976298562c6cd-067a-433f-b693-677bdb1a8ee0 There’s no way to prevent or get rid of HAE if you carry one of the genetic changes that causes it, but you may be able to control your symptoms by identifying possible triggers and taking prescribed medications.e60dc2a1-f33c-4a05-9b50-8e3e8e5976298562c6cd-067a-433f-b693-677bdb1a8ee0
HAE Causes: A Handful of Genetic Changes The Genetics of HAE Hereditary angioedema occurs as a result of a genetic change. The mechanism of an HAE attack varies depending on which genetic change you have.e60dc2a1-f33c-4a05-9b50-8e3e8e597629a1b6aec7-ba82-41a6-8dd5-38225ea7856a There are two known mutations — in the SERPING1 gene and the F12 gene — but scientists suspect there are also other as yet unidentified genes that cause HAE. The type of treatment you are prescribed will be influenced by which genetic change you carry.e60dc2a1-f33c-4a05-9b50-8e3e8e597629a1b6aec7-ba82-41a6-8dd5-38225ea7856a Changes in the SERPING1 Gene Cause HAE Types 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 inhibitor, which is important for controlling swelling.e60dc2a1-f33c-4a05-9b50-8e3e8e597629a1b6aec7-ba82-41a6-8dd5-38225ea7856a In type 1 HAE, your body does not make enough C1 inhibitor. With type 2, your body makes enough of the protein, but it doesn’t work properly.e60dc2a1-f33c-4a05-9b50-8e3e8e597629a1b6aec7-ba82-41a6-8dd5-38225ea7856a Without normal and functional amounts of C1 inhibitor, the body generates too much bradykinin — a protein peptide. Bradykinin causes excessive fluid to leak through the walls of body tissues, which leads to inflammation and episodes of swelling.e60dc2a1-f33c-4a05-9b50-8e3e8e59762995d90af9-e634-45cf-8f80-cd5e85dd5bafe60dc2a1-f33c-4a05-9b50-8e3e8e5976297708e641-e1ac-4f56-b8f1-25b4be3c40b2 Changes in the F12 Gene Cause HAE Type 3 Type 3 HAE is an extremely rare form of the disease, and the exact prevalence isn’t known. Scientists believe that some cases of type 3 HAE are caused by changes in the F12 gene.e60dc2a1-f33c-4a05-9b50-8e3e8e597629a1b6aec7-ba82-41a6-8dd5-38225ea7856a In type 3 HAE, C1 inhibitor levels and functioning are normal, but the F12 changes cause dysregulation in the bodily system that makes a protein called coagulation factor XII, which plays a role in stimulating inflammation and producing bradykinin.e60dc2a1-f33c-4a05-9b50-8e3e8e597629a1b6aec7-ba82-41a6-8dd5-38225ea7856a Other cases of type 3 HAE have no known causes. Researchers believe unidentified genes play a role.e60dc2a1-f33c-4a05-9b50-8e3e8e597629e0bccc30-2335-4ab8-87b4-bfe67114be3ce60dc2a1-f33c-4a05-9b50-8e3e8e59762974e44194-be9f-4065-81e6-70d2c3e8cba3
HAE: How Is It Passed Down? HAE is 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.e60dc2a1-f33c-4a05-9b50-8e3e8e597629738cb808-6baa-4748-9705-800a759d17e0e60dc2a1-f33c-4a05-9b50-8e3e8e597629bae1246a-f5f4-4e0c-b0ae-4560e9d97fd0 HAE can also develop in people with no family history of it, if a spontaneous gene change happens during conception.e60dc2a1-f33c-4a05-9b50-8e3e8e597629738cb808-6baa-4748-9705-800a759d17e0e60dc2a1-f33c-4a05-9b50-8e3e8e597629bae1246a-f5f4-4e0c-b0ae-4560e9d97fd0
Testing for HAE Testing for HAE If HAE runs in your family, you might want to consider getting tested for it. Or, if you have the disease, you might decide that you want your family members to get tested. Even though this is a disease that is caused by a genetic change, genetic testing, which analyzes changes in genes, isn’t needed to confirm a diagnosis of HAE . The simplest form of testing involves a blood test that measures levels of C1 inhibitor or how well this protein works in your body, and sometimes other biomarkers of the disease in your bloodstream. Other testing includes monitoring C4 protein or D-dimer protein levels during acute attacks, according to a review.e60dc2a1-f33c-4a05-9b50-8e3e8e597629c30b514a-ac97-4f47-975d-e69caf0a64cf Genetic testing can be used as a follow-up test to confirm the results of the blood test, if necessary. Genetic testing is limited in that it does not predict disease progression, so it cannot tell you how your symptoms will progress.e60dc2a1-f33c-4a05-9b50-8e3e8e597629c30b514a-ac97-4f47-975d-e69caf0a64cf 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.e60dc2a1-f33c-4a05-9b50-8e3e8e597629c30b514a-ac97-4f47-975d-e69caf0a64cf
What Are the Early Signs of an HAE Attack? Symptoms and Triggers Most HAE attacks occur when your body needs the C1 inhibitor but can’t make enough of the protein or use it properly.e60dc2a1-f33c-4a05-9b50-8e3e8e597629b59b73f0-fea6-44ca-b5b8-df23e9b53bebe60dc2a1-f33c-4a05-9b50-8e3e8e597629cf302a8b-2fd9-4dd4-964c-7e42f5d9b60e Attacks may involve severe swelling in the skin (typically of the face, limbs, genitals, or buttocks), gastrointestinal tract, or airway.e60dc2a1-f33c-4a05-9b50-8e3e8e59762910a68c74-3eae-42de-b1f2-c5a632900afae60dc2a1-f33c-4a05-9b50-8e3e8e5976292a757968-4bc2-460b-9b15-3eb887460364 While it’s hard to predict when an HAE episode will happen, some people report symptoms that forecast a problem. These signs can occur several hours or even a full day before the attack. Common signs of an HAE attack include:e60dc2a1-f33c-4a05-9b50-8e3e8e5976299c7d8343-e19a-4423-ab21-54fceac2bde3e60dc2a1-f33c-4a05-9b50-8e3e8e5976292a757968-4bc2-460b-9b15-3eb887460364 Fatigue Irritability Weakness Nausea Pink rings or rash
What Are HAE Attack Triggers? Certain factors may prompt an HAE attack. These include:e60dc2a1-f33c-4a05-9b50-8e3e8e597629a9189298-824c-4f8d-bb04-90c40002c916e60dc2a1-f33c-4a05-9b50-8e3e8e597629b63ea270-f7b9-40f7-8d2a-516580111dcd 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 Medicines 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.e60dc2a1-f33c-4a05-9b50-8e3e8e59762990f67eab-1850-4b31-be1b-309f03f5dffc Having a dental procedure may also trigger an HAE episode. Some people also report swelling after engaging in activities such as:e60dc2a1-f33c-4a05-9b50-8e3e8e597629a9189298-824c-4f8d-bb04-90c40002c916 Typing or writing Pushing a lawn mower Shoveling Hammering Other physical activities
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. For instance, try to keep your stress levels low. Also, talk to your doctor before taking any new medications or having a surgical procedure that could provoke a swelling episode. And take all your prescribed preventive medicines.e60dc2a1-f33c-4a05-9b50-8e3e8e5976293656048d-cef9-47f0-8612-4525b3b3266a Some people keep a journal of their attacks. This can help you better identify triggers.e60dc2a1-f33c-4a05-9b50-8e3e8e59762985037c05-1067-4838-a43e-89cd30287c1a
The Takeaway Hereditary angioedema is a genetic condition that causes repeated episodes of severe, painful swelling, typically in the face, hands, feet, or airway. Triggers 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.