Shonna’s Summaries: “Hereditary alpha-tryptasemia and monoclonal mast cell disorders”

by Shonna Snyder

This blog post is part of a regular series of blog posts aimed at summarizing academic journal articles, in order to provide the community with more accessible information, based on recently published scientific research, to share with their care teams.

This week we are exploring the article by Chantran and Arock entitled Hereditary alpha-tryptasemia and monoclonal mast cell disorders [1] to learn more about this symptom modifier and its’ relationship to mast cell diseases (MCD).

It is important to be screened for hereditary alpha tryptasemia (HaT) if you are in the diagnostic process or treatment for a MCD. Let’s dig into this topic a bit more.

First, what is HαT?

“Hereditary alpha-tryptasemia is an autosomal dominant genetic trait caused by increased germline copies of TPSAB1 encoding alpha-tryptase” [2].  Whoa, that’s a mouthful… let’s break it down and define these terms in order to understand what this means. The National Human Genome Research Institute explains:

An autosome is a non-sex chromosome.  Autosomal then means that the gene in question is located on one of the chromosomes that are not related to your sex (XX or XY). There are 22 pairs of these non-sex chromosomes.

Dominant means that one parent’s genes cause you to have certain traits, such as your eye color.  In the disease process, a single copy of a mutated gene (from one parent) can cause a disorder.

“[So] a child of a person affected by an autosomal dominant condition has a 50% chance of being affected by that condition via inheritance of a dominant allele. [Where] by contrast, an autosomal recessive disorder requires two copies of the mutated gene (one from each parent) to cause the disorder” [3].

Having “increased germline copies of TPSAB1 encoding alpha-tryptase” means that you have extra copies of the TPSAB1 gene. When these extra copies cause HαT, you will have elevated levels of alpha-tryptase, a protein, in your blood, which will show up on a basal serum tryptase (bST) blood test. Some people have extra β-tryptase copies, but these do not cause HαT or elevated bST and so far, researchers have not found that having additional β-tryptase copies is associated with clinical findings.

Second, if you have HαT, how does that relate to MCD?

HαT alone is associated with symptoms that are like MCD symptoms, such as idiopathic anaphylaxis, more severe allergic reactions, flushing, and GI complaints such as diarrhea. But the reality is that to be diagnosed with a MCD there are criteria you must meet.  Your doctor will look at certain markers, including your levels of bST, mast cells in your bone marrow or other organs, and other diagnostic markers. You may have HαT, and this changes the diagnostic workup and criteria for the diagnosis of SM. 

If you have HαT, you will probably have an elevated bST (remember our explanation above). About 5% of the population has this genetic trait and we do see more HαT in those diagnosed with MCD- particularly adults with SM- than the general population (between 12-21%).

If you have both MCD and HαT, you may also be more prone to having anaphylaxis with your allergies as it’s been reported that individuals with both are twice as likely to experience anaphylaxis than individuals with MCD only. The primary trigger for anaphylaxis in a few studies was the stings from bees, wasps, or ants, known as Hymenoptera stings.  Some patients also have issues with vibrations causing skin rashes or other symptoms.

What should you do about your HαT diagnosis?

As mentioned above, it is important that you undergo the testing for HαT.  Once you have been diagnosed with it, there are a few things that are recommended.

1. You should also learn more about this life-threatening condition. See our page for more information on anaphylaxis (Anaphylaxis).
2. If you have a history of food or venom allergy or anaphylaxis, you should always carry two devices for administering epinephrine (either by auto-injector or intra-nasal) for the emergency situation you could find yourself in during anaphylaxis.  See our treatment page for more information on epi-pens (Medications for Mast Cell Diseases).

What should your doctors know about HαT?

It is important to talk to your doctor about testing you for HαT if you are in the diagnostic journey for MCD or already diagnosed. They should understand that HαT is a symptom modifier and might make your MCD symptoms worse. You will want to discuss your risk of anaphylaxis with them and discuss your emergency room protocol as well as a prescription for two doses of epinephrine.  

Acknowledgements: We’d like to extend our thanks to Dr. Jonathon Lyons for his help with reviewing and editing this blog post.

References:

1.           Chantran Y, Arock M. Hereditary alpha-tryptasemia and monoclonal mast cell disorders. Front Allergy. 2025;6:1600680. Frontiers | Hereditary alpha-tryptasemia and monoclonal mast cell disorders

2.           Lyons JJ. Hereditary Alpha Tryptasemia: Genotyping and Associated Clinical Features. Immunol Allergy Clin North Am. 2018;38(3):483-95. 3.           Institute NHGR. Autosomal dominant disorder 2025 [updated July 8, 2025. Available from: https://www.genome.gov/genetics-glossary/Autosomal-Dominant-Disorder.