What is Hereditary Alpha Tryptasemia?

A person in a green sweater reads a hardcover book at a table. A clear glass of frothy coffee sits nearby. The background is softly blurred, indicating a cozy, indoor setting.

Hereditary alpha tryptasemia (HαT) is a genetic trait. It was first identified in 2014. What causes it – elevated basal serum tryptase levels – was determined two years later. HαT occurs in 5.5% of general populations where it has been studied. However, the majority of people with HαT are white.

People with this genetic trait develop increased alpha tryptase levels. Tryptase is a protein found in high concentrations around blood vessels and in mast cells. It can make its way into the bloodstream. Mast cells are born in the bone marrow, but they are not capable of making tryptase or causing symptoms until they move to other parts of the body. This is when they can grow into fully functioning mast cells. An increase in tryptase levels is a marker of mast cell activation. It plays a major role in allergic reactions.

During allergic reactions, mediators from mast cells (including tryptase) enter your bloodstream. People with HαT have elevated tryptase levels, even if they aren’t having an allergic reaction. This can lead to a host of symptoms. They may be at risk for a severe or life-threatening allergic reaction, or anaphylaxis. Many people are not aware they have HαT. About one-third of people with HαT show symptoms. The remaining two-thirds show few symptoms or no symptoms at all.

Since HαT is genetic, there is at least a 50% chance the trait will be passed on to a child.

HαT is more common in people who have mastocytosis. This is a condition where increased levels of mast cells cause symptoms that mimic severe allergic reactions, often without a known cause. It is believed the presence of HαT may cause mastocytosis symptoms to be more severe. Research is ongoing.

Research so far has found no direct link between HαT and asthma, allergic rhinitis, GERD, atopic dermatitis, or irritable bowel syndrome. It is possible that HαT could worsen allergic diseases if they are untreated.

A woman with shoulder-length blond hair appears to be in pain, holding her left shoulder with her right hand while closing her eyes. She is wearing a gray sweater and standing in a softly lit room.

Signs and symptoms of hereditary alpha tryptasemia

HαT-associated symptoms can vary from person to person. People with HαT may show the following symptoms:

  • Skin. Rashes, flushing
  • Digestive. Stomach or abdominal pain, bloating, diarrhea or constipation, reflux, heartburn, difficulty swallowing (some of these symptoms may first be diagnosed as irritable bowel syndrome)
  • Heart. Fast heartbeat, blood pressure changes, fainting
  • Muscle and bones. Joint pain, back pain, being double-jointed, scoliosis
  • Mental health. Brain fog, anxiety, panic attacks
  • Chronic pain
  • Frequent allergic reactions
  • Severe or life-threatening anaphylaxis

HαT may not be the cause of these symptoms. But it is likely the symptoms are worsened by HαT.

People with HαT have elevated tryptase levels. This may put them at risk for severe mast cell-mediated allergic reactions, including anaphylaxis.

Triggers may include an insect sting, certain foods, certain medications, or even skin friction or vibration (such as from a lawnmower). When people with insect venom allergy have elevated tryptase, they tend to have more frequent severe reactions when stung. People with food allergies with elevated tryptase also tend to have more severe reactions.

Anaphylaxis can affect multiple body systems. These may include the skin (itchy hives), digestive tract (swelling of the mouth, tongue or throat, nausea, vomiting, diarrhea), respiratory system (shortness of breath), and heart (increased heart rate).

In some cases, a severe allergic reaction may happen without an apparent cause. This is called idiopathic anaphylaxis. HαT is more common among people with idiopathic anaphylaxis.

An elderly woman wearing glasses sits across from a male doctor in a white coat. The doctor is holding a clipboard and appears to be discussing medical information with her.

How is hereditary alpha tryptasemia diagnosed?

Your doctor will evaluate you for clinical features of HαT (including medical history) and take a blood test to measure for elevated serum tryptase levels. This test should be done when you have minimal or no symptoms. The test should not be done until at least 24 hours have passed after symptoms of a recent allergic reaction. The presence of symptoms may affect the test results.

If the blood test shows elevated tryptase levels, your doctor should follow up with a special genetic test. This test checks to see if you inherited extra copies and versions of the alpha tryptase gene. The test is called tryptase genotyping (also called a “Tryptase CNV test” or “HαT test”).

Misdiagnosis and delayed diagnosis are common with HαT. Some people may have both HαT and mastocytosis, which can complicate the diagnosis. Other people may have symptoms not caused by HαT, especially if the symptoms do not respond to medications that treat mast-cell related allergic reactions.

It’s important to advocate for yourself for continued evaluation if problems persist after treatment.

A doctor with gray hair and a white coat is talking to a patient who is signing a document at a desk. The doctor has a stethoscope around her neck. There are medicine bottles and a laptop on the desk, with shelves in the background.

Treatment for hereditary alpha tryptasemia

HαT is a genetic trait and no medications are currently available that can inhibit or block tryptase itself. Treatments for HαT-related symptoms are available. These treatments may require some trial and error until the best option is identified.

Treatments may include:

  • Allergy medicines (antihistamines)
  • Mast cell stabilizers
  • Corticosteroids
  • Epinephrine (to treat anaphylaxis)

Some doctors may recommend an anti-IgE medication such as the biologic omalizumab (Xolair®). But currently this is not an FDA-approved treatment for HαT. One study of allergic asthma patients found that having more alpha tryptase was linked to a better response rate to omalizumab.

Talk with your doctor about what treatment is best for you.

If you have HαT and you are at risk for anaphylaxis, make sure you know your triggers and how to avoid them. Epinephrine is the first line of treatment for anaphylaxis. If you are prescribed epinephrine to treat anaphylaxis, keep it with you at all times. You will need to carry two devices of epinephrine in case symptoms return after the first dose. If symptoms are severe, they worsen or persist, or they come back, administer the second dose. Then seek emergency medical treatment.

Three young women sit together on outdoor steps, looking at a tablet. They appear engaged and are dressed casually. The woman in the middle wears a white shirt, while the others wear a green top and a striped shirt, respectively.

Is hereditary alpha tryptasemia a form of mast cell disease?

HαT is often considered a type of mast cell disorder. The two conditions have similar symptoms. They respond to the same types of treatment. However, having HαT may not necessarily mean there’s a mast cell problem. And it may not cause allergic disease or another medical issue. More research is needed to determine how mast cells contribute to HαT.

Questions & Answers (Q&A) on Hereditary Alpha Tryptasemia (HαT)

Here are some common questions about HαT. Please email the editor if you have other questions not listed below..

Most people with high blood tryptase levels have HαT. The only way to know for sure if you have HαT is to have a special genetic test that counts the copies and versions of tryptase you have inherited.

Multiple studies in the United States and European Union have found people with HαT are more likely to have systemic mastocytosis or another clonal mast cell disease. As a result, they are more likely to experience symptoms and be at risk for anaphylaxis.

People with HαT or a mast cell disease should talk with their doctor about both conditions. More people with mast cell diseases have the HαT trait than in the general population. This includes systemic mastocytosis, idiopathic anaphylaxis, and mast cell activation syndrome (MCAS).

Your doctor can determine appropriate HαT testing and, if needed, treatment.

Yes. Based on associated clinical features, HαT is linked with all forms of MCAS. However, HαT is not believed to cause MCAS. Instead, it is believed that what causes mast cells to activate is made worse by HαT.

Make an appointment with a doctor to discuss testing for HαT. You may want to see a specialist for testing. Board-certified allergists are specialists who can test you for HαT.

Idiopathic MCAS occurs when there is no known trigger. When you don’t know what is causing symptoms, MCAS can be frustrating to manage. Medications can help reduce the severity and frequency of symptoms.

Mastocytosis is a mast cell disorder. It involves several types, from mild to severe. Hereditary alpha tryptasemia (HαT) is a genetic trait that can cause frequent and severe mast cell-mediated reactions like anaphylaxis. HαT has been linked to mastocytosis, MCAS with idiopathic anaphylaxis, and severe reactions to stinging insects.

For support and further information about mast cell diseases, please visit The Mast Cell Disease Society.

Mast Cell Disease Podcasts

Illustration of silhouettes arranged in a circle, with one silhouette in the center. The central figure is colorful with various dots, while the others are plain blue. The background features concentric circles.

Living with Systemic Mastocytosis

Reading Time: 2 minutes
Our latest podcast gets the patient perspective on diagnosing and managing systemic mastocytosis, one of the more common mast cell…
Illustration of a human silhouette with colorful dots, surrounded by medical items like pills, a bottle labeled "Rx", a syringe, and a medical vial. The background has concentric circles, suggesting a focus on medicine or health.

How are Mast Cell Diseases Treated?

Reading Time: 18 minutes
Our podcast hosts focus on mast cell disease treatment and the multidisciplinary approach that can be helpful in managing these…
Illustration of a test tube filled with a colorful, layered liquid, with pink, yellow, and purple hues. The tube is surrounded by concentric circles on a light blue gradient background.

How to Diagnose Mast Cell Disease

Reading Time: 19 minutes
Our podcast co-hosts Kortney Kwong Hing and Payel Gupta, MD, welcome allergist Joshua Milner, MD, to discuss the complexities of…

Reviewed by:
Jonathan Lyons, MD, is a board-certified allergist and immunologist at the University of California, San Diego. He is chief of the Translational Allergic Immunopathology Unit in Laboratory of Allergic Diseases at the National Institutes of Allergy and Infectious Diseases (NIAID). Dr. Lyons has received NIAID Merit Wards for his groundbreaking work in characterizing pathways leading to increased mast cell hyperactivity and anaphylaxis in people with hereditary alpha tryptasemia.

Supported by: 

Logo of Blueprint Medicine featuring the company name in a bold, modern font. A stylized DNA strand forms part of the letter "b," incorporating shades of blue.