MINI REVIEW article

Front. Allergy

Sec. Genetics and Epidemiology

Volume 6 - 2025 | doi: 10.3389/falgy.2025.1598309

This article is part of the Research TopicHereditary alpha-tryptasemia: ten years onView all 5 articles

Non allergic gastrointestinal manifestations of hereditary alpha-tryptasemia

Provisionally accepted
  • The University of Utah, Salt Lake City, Utah, United States

The final, formatted version of the article will be published soon.

Hereditary alpha-tryptasemia (HT) is an autosomal dominant genetic trait characterized by elevated basal serum tryptase due to increased TPSAB1 gene copy numbers. Affecting approximately 4-6% of the Caucasian population, HT is associated with mast cellmediated symptoms, including cutaneous reactions, anaphylaxis, and functional gastrointestinal (GI) disorders. While the prevalence of HT in various disorders of gut brain interaction (DGBI)is unknown, individuals with HT exhibit GI disturbances.Mast cells, present throughout the GI tract, release mediators like histamine and prostaglandins, affecting gut motility, secretion, and permeability. Mast cell mediated activation of proteaseactivated receptors may contribute to gut barrier dysfunction, exacerbating the gastrointestinal symptoms. HT-related GI symptoms are commonly misdiagnosed as other GI conditions, highlighting the need for increased awareness and further research into its pathophysiology and clinical impact.There are no randomized controlled trials on therapy for HT mediated GI symptoms. Current treatment options are based on expert opinion, observational studies, and case reports. Effective therapies parallel those given for clonal mast cell disorders, primarily consisting of antihistamines and mast cell stabilizers. Further research is necessary to delineate the pathophysiology of HT in the gastrointestinal tract so that targeted therapies may be developed. Herein, we aim to describe the pathophysiology, clinical manifestations, diagnostic features, and current/future therapeutic options for patients suffering from HT-mediated GI symptoms.

Keywords: Hereditary alpha tryptasaemia, gut brain axis, gastrointestinal disease, mast cell, Mastocytosis

Received: 22 Mar 2025; Accepted: 21 May 2025.

Copyright: © 2025 Vainer and Peterson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dylan Vainer, The University of Utah, Salt Lake City, 84112, Utah, United States
Kathryn Peterson, The University of Utah, Salt Lake City, 84112, Utah, United States

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