The Steps To a Hereditary Angioedema (HAE) Diagnosis
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How Is Hereditary Angioedema (HAE) Diagnosed?

How Is Hereditary Angioedema (HAE) Diagnosed?
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Updated on July 16, 2025
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If you have hereditary angioedema (HAE), getting an accurate diagnosis can be tricky.

Because HAE is so rare, many doctors aren’t familiar with the disease. Also, your symptoms can mimic those of other conditions, which further complicates the process.

To receive an HAE diagnosis, you’ll need to have a physical exam as well as blood tests.

Making a HAE Diagnosis: Standard Blood Tests

If your doctor thinks you might have HAE, he or she will probably first ask about your symptoms and family history. It’s important to know that you could have HAE even if your family members don’t.

The next step is to perform lab tests to measure levels of the proteins C4, C1 esterase inhibitor, and C1 esterase functional level.

The three blood tests used to confirm if you have HAE type 1 or type 2 are:

  • C1-inhibitor quantitative (antigenic)
  • C1-inhibitor functional
  • C4
Sometimes more than one of these tests is used to make a more precise diagnosis.

Most doctors recommend waiting until children are at least 1 year old before testing their C1 inhibitor levels.

Genetic Testing: Becoming More Reliable

Most cases of HAE type 1 and 2 are caused by a gene mutation that affects the SERPING1 gene, while HAE type 3 is affected by genes F12, PLG, ANGPT1, and KNG1. However, genetic testing is not a simple process for this disease.

Genetic testing does not always give clear answers, but it is more reliable in detecting the most common forms of the disease involving HAE-1 or HAE-2. And it can detect certain mutations that standard testing can miss. It offers less in confirming rare cases with normal C1-inhibitor levels.

Genetic testing cannot predict disease progression or severity. And a recent study showed that while most doctors think genetic testing would help, barriers to using it include insurance, cost, and the availability of genetic counseling to interpret the tests.

Some doctors might recommend genetic testing in children under 1 year old because they can get false results on standard blood tests.

Misdiagnosis and Delayed Diagnosis Are Common Problems

People with HAE are often misdiagnosed as having another medical problem. In one survey of 313 patients, 65 percent of those with HAE reported being misdiagnosed before a doctor accurately identified their condition.

HAE is commonly mistaken for:

In the past, HAE diagnosis delays ranged from 10 to 22 years. Today, about 40 percent of people with HAE are diagnosed within the first three years. About 33 percent of people still face delays of 10 years or longer.

A misdiagnosis or delayed diagnosis can lead to serious consequences because people with HAE may not receive the proper treatment that can help their condition. About 19 percent of people also undergo unnecessary medical procedures, including appendix removal, because of a misdiagnosis.

In the most extreme cases, a missed diagnosis can be deadly. In studies, death rates from an HAE throat swelling episode can be as high as 30 percent if patients don’t receive treatment.

When Is HAE Typically Diagnosed?

The age of onset for people with HAE varies. Studies show that about one-half report their first symptoms by age 7, and more than 66 percent have symptoms by age 13.

Typically, the number and severity of attacks increase during a person’s teenage years.

Because many people with HAE experience diagnosis delays, symptoms can start long before an official diagnosis is made.

What to Do After a Diagnosis

If you receive an HAE diagnosis, you may want to recommend that your close family members get tested, too, since HAE can run in families.

Once you’re diagnosed, it’s important to find a doctor who has experience treating the disease. You can find a specialist by contacting advocacy organizations or experts who appear in published medical journals. Board-certified allergists and immunologists are trained to manage and treat patients of all ages with HAE.

 The U.S Hereditary Angioedema Association offers a list of physicians around the country who treat HAE.

A diagnosis of HAE can be scary, and you’ll probably have a lot of questions. So along with a copy of your test results, bring a list of questions to your first doctor’s appointment.

Per Cleveland Clinic, here are some questions to ask your doctor:

  • What is HAE? Why do I have it?
  • Do I need any more medical tests?
  • How serious is this disease?
  • What will my life be like with HAE?
  • What symptoms should I watch out for?
  • Are there any ways to prevent an HAE attack?
  • What treatments are available?
  • What are the treatment side effects?
  • How often will I need to come to the doctor?
  • Should my family members be tested for HAE?
  • Where can I find support?

Taking charge of your health is important. Make sure you’re comfortable talking to your doctor about your condition and all available treatment options. If you don’t feel like your provider is a good fit, try making an appointment with another specialist.

The Takeaway

  • Blood tests are the standard method for determining an HAE diagnosis, but genetic testing is becoming more established.
  • Misdiagnosing HAE for gastrointestinal issues, allergic reaction, or appendicitis is common and can lead to serious consequences. Some patients undergo unnecessary treatments or surgeries because of a misdiagnosis.
  • After a diagnosis, find a doctor experienced in treating the disease.
  • It’s also important to alert immediate family members to give them the option to get tested, even if they are asymptomatic.
EDITORIAL SOURCES
Everyday Health follows strict sourcing guidelines to ensure the accuracy of its content, outlined in our editorial policy. We use only trustworthy sources, including peer-reviewed studies, board-certified medical experts, patients with lived experience, and information from top institutions.
Resources
  1. Getting an Accurate HAE Diagnosis. Discover HAE.
  2. About Hereditary Angioedema. U.S. Hereditary Angioedema Association.
  3. Sinnathamby ES et al. Hereditary Angioedema: Diagnosis, Clinical Implications, and Pathophysiology. Advances in Therapy. January 7, 2023.
  4. Parenting a Child With HAE. U.S. Hereditary Angioedema Association.
  5. Rozevska M et al. Hereditary or Acquired? Comprehensive Genetic Testing Assists in Stratifying Angioedema Patients. Allergy, Asthma & Clinical Immunology. March 30, 2024.
  6. Laney DA et al. Health Care Providers’ Experiences With Genetic Testing in Patients at Risk For Hereditary Angioedema. Journal of Allergy and Clinical Immunology: Global. May 2025.
  7. Hereditary Angioedema Diagnosis. Discover HAE.
  8. Hereditary Angioedema. Allergy & Asthma Network.
  9. Questions to Ask Your Doctor. Cleveland Clinic.
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Asal Naderi, MD

Medical Reviewer

Asal Naderi, MD, is an assistant clinical professor of allergy and immunology at the Keck School of Medicine at the University of Southern California. Her areas of focus include allergic rhinitis, asthma, chronic sinusitis with nasal polyposis, chronic urticaria, angioedema, food allergy, drug allergy, and primary immunodeficiencies.

She received her bachelor's degree from the University of California Los Angeles and then received her medical degree from Saint Louis University. She completed her internal medicine residency at University of California Irvine, and her fellowship at the University of California Irvine. She has been a principal investigator in clinical trials for asthma as well as chronic sinusitis.

Outside of the office, she enjoys exercising, cooking and spending time with her family and friends.

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Julie Lynn Marks

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Julie Marks is a freelance writer with more than 20 years of experience covering health, lifestyle, and science topics. In addition to writing for Everyday Health, her work has been featured in WebMD, SELF, Healthline, A&E, Psych Central, Verywell Health, and more. Her goal is to compose helpful articles that readers can easily understand and use to improve their well-being. She is passionate about healthy living and delivering important medical information through her writing.

Prior to her freelance career, Marks was a supervising producer of medical programming for Ivanhoe Broadcast News. She is a Telly award winner and Freddie award finalist. When she’s not writing, she enjoys spending time with her husband and four children, traveling, and cheering on the UCF Knights.

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