Hereditary Alpha Tryptasemia
Open accessAbstract
Hereditary alpha tryptasemia is an autosomal dominant genetic trait caused by increased germline copies of TPSAB1 encoding alpha-tryptase. Individuals with this trait have elevated basal serum tryptase, and may present with associated multisystem complaints. Both basal serum tryptase levels and severity of clinical symptoms display a gene-dose relationship with TPSAB1, whereby higher tryptase levels and greater symptom severity are correlated with increasing numbers of alpha-encoding TPSAB1. As the functional effects of increased basal serum tryptase and/or altered tryptase gene expression are elucidated, greater insights will be gained into the symptoms associated with hereditary alpha tryptasemia and their potential therapy.
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In some cases, patients with HαT do present with a clinical picture dominated by mediator-related symptoms (i.e., vibratory urticaria, flushing, abdominal cramps, headache, dysautonomia, etc.).
“In some cases, patients with HαT do present with a clinical picture dominated by mediator-related symptoms (i.e., vibratory urticaria, flushing, abdominal cramps, headache, dysautonomia, etc.) [15,16,45].”
From Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders (2023) · cites this paper as [15]
The Associated clinical features section (page unavailable) reports flushing, vibration-triggered skin symptoms, gastrointestinal complaints, and symptoms suggestive of autonomic dysfunction in people with HαT. It calls the skin symptoms suggestive of mast-cell mediator release, but says the episodes were not sufficiently studied to confirm they were mast-cell-related. The claim’s characterization of the clinical picture as dominated by mediator-related symptoms is therefore stronger than the source supports. (LLM, conf=0.86)
Experimental — accuracy not yet measuredVarious clinical conditions, including dysautonomia with postural orthostatic hypotension, flushing, gastrointestinal hypomotility, joint hypermobility, vibratory urticaria, irritable bowel syndrome, chronic musculoskeletal pain, retained primary dentition, and allergic disorders, were initially reported in patients with hereditary alpha-tryptasemia.
“Initially, various clinical conditions, including dysautonomia with postural orthostatic hypotension, fl ushing, gastrointestinal hypomotility, joint hypermobility, vibratory urticaria, irritable bowel syndrome, chronic musculoskeletal pain, retained primary dentition, and allergic disorders, were reported in patients with H a T. 120,121,125-127”
From Selecting the Right Criteria and Proper Classification to Diagnose Mast Cell Activation Syndromes: A Critical Review (2021) · cites this paper as [125]
The Associated clinical features section (page unavailable) reports orthostatic hypotension and other autonomic symptoms, flushing, joint hypermobility, IBS, chronic pain, retained primary dentition, and allergic reactions in people with hereditary alpha-tryptasemia. It also reports urticaria and vibration as a trigger for cutaneous symptoms, but does not clearly identify vibratory urticaria. The copy does not report gastrointestinal hypomotility or specify that the chronic pain was musculoskeletal. (LLM, conf=0.86)
Experimental — accuracy not yet measuredHereditary alpha tryptasemia (HαT) is characterized by an increased alpha coding TPSAB1 copy number and is associated with a baseline tryptase value above 8 ng/mL.
“A genetic trait, hereditary alpha tryptasemia, characterized by an increased alpha coding TPSAB1 copy number is associated with a baseline value above 8 ng/mL.”
From Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders (2023) · cites this paper as [15]
HαT may account for elevated serum tryptase in the absence of clonal mast cell disorders.
“Hereditary alpha-tryptasemia (HαT) is an autosomal dominant genetic trait of an increased copy number of the alpha-coding (of ≥2) TPSAB1-gene [15,16], which may account for elevated serum tryptase in the absence of clonal mast cell disorders.”
From Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders (2023) · cites this paper as [15]
The growing knowledge of HαT, a germline condition causing increase in BST, has not fully elucidated clinical consequences.
“growing knowledge of hereditary alpha-tryptasemia (HαT), a germline condition causing increase in BST with not fully elucidated clinical consequences (4–6).”
From Defining “Normal” basal serum tryptase levels: a context-dependent approach to improve diagnostics in systemic mastocytosis (2025) · cites this paper as [4]
Lyons et al. first described HαT, an autosomal dominant condition resulting from multiplication of TPSAB1 gene encoding alpha isoform.
“Around a decade ago, Lyons et al. (4, 11) first described a genetic trait known as HαT, an autosomal dominant condition resulting from the multiplication of the TPSAB1 gene (Figure 1) encoding the alpha isoform of tryptase.”
From Defining “Normal” basal serum tryptase levels: a context-dependent approach to improve diagnostics in systemic mastocytosis (2025) · cites this paper as [4]
HαT is an autosomal dominant germline condition caused by increased copies of the TPSAB1 gene encoding the alpha isoform of tryptase.
“hereditary alpha-tryptasemia (HαT), an autosomal dominant germline condition that consists in the increase of the number of copies of the TPSAB1 gene encoding the alpha isoform of tryptase”
From Defining “Normal” basal serum tryptase levels: a context-dependent approach to improve diagnostics in systemic mastocytosis (2025) · cites this paper as [4]
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Clinical Impact of Inherited and Acquired Genetic Variants in Mastocytosis
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World Health Organization Classification and Diagnosis of Mastocytosis
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The Who, What, Where, When, Why, and How of Drug Desensitization
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Severe food allergy reactions are associated with α-tryptase
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Mast cell disorders are associated with decreased cerebral blood flow and small fiber neuropathy
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Mast cell activation in the context of elevated basal serum tryptase: genetics and presentations
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Self-citationReview and updates on systemic mastocytosis and related entities
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Clinical response to omalizumab in patients with hereditary α-tryptasemia
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Drug Desensitizations for Chemotherapy: Safety and Efficacy in Preventing Anaphylaxis
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Lipidomic analysis of urinary exosomes from hereditary α‐tryptasemia patients and healthy volunteers
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Secretory and Membrane-Associated Biomarkers of Mast Cell Activation and Proliferation
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Targeting Mast Cells with Biologics
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Self-citationAlpha-tryptase as a risk-modifying factor for mast cell–mediated reactions
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Self-citationMast Cells and Basophils in IgE-Independent Anaphylaxis
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Assessment of Osteoporosis and Fracture Risk in Mastocytosis within a North American Cohort
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Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders
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“In some cases, patients with H α T do present with a clinical picture dominated by mediator-related symptoms (i.e., vibratory urticaria, flushing, abdominal cramps, headache, dysautonomia, etc.) [15,16,45].”
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Peri-Operative Anaphylaxis—An Investigational Challenge
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Self-citationGene–environment interactions in primary atopic disorders
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Idiopathic Anaphylaxis: A Form of Mast Cell Activation Syndrome
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Extrinsic and Intrinsic Modulators of Anaphylaxis
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The clinical features of hereditary alpha-tryptasemia
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Idiopathic anaphylaxis: Diagnosis and management
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Basal serum tryptase: A critical reconsideration of reference values
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Current Challenges in the Diagnosis of Pediatric Cutaneous Mastocytosis
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Hereditary α-tryptasemia is Associated With Anaphylaxis to Antibiotics and Monoclonal Antibodies
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Self-citationChallenges in applying diagnostic criteria for systemic mastocytosis
Boggs, N. A., Sun, X., Lyons, J. J., McMurray, J. C., Rose, D. M., Pryor, E. M., Metcalfe, D. D., & Marić, I. (2023) · Blood Advances · doi:10.1182/bloodadvances.2023009826 · Cited by 14 · see citing works
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Self-citationHypertryptasemia and Mast Cell-Related Disorders in Severe Osteoporotic Patients
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Reproducibility of Symptom Sequences Across Episodes of Recurrent Anaphylaxis
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Mast Cell Activation Syndrome and Gut Dysfunction: Diagnosis and Management
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Challenges in Drug and Hymenoptera Venom Hypersensitivity Diagnosis and Management in Mastocytosis
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Clinically accessible amplitude-based multiplex ddPCR assay for tryptase genotyping
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Self-citationAnaphylaxis: Advances in the Past 10 Years
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A Challenge for Allergologist: Application of Allergy Diagnostic Methods in Mast Cell Disorders
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Tryptase: The Silent Witness of Past and Ongoing Systemic Events
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Update on desensitization to chemotherapeutics and biologicals
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Self-citationPathogenic and diagnostic relevance of KIT in primary mast cell activation disorders
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Expanding the Immunologic and Neuronal Landscape of IgE‐Mediated Anaphylaxis
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Dosage de la tryptase : un guide d'utilisation pour le clinicien
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Mast cell activation syndrome: Myths and realities
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Genetic Variants Leading to Urticaria and Angioedema and Associated Biomarkers
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Self-citationPatients with elevated basal tryptase serum levels should be tested for hereditary alpha-tryptasemia
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Hypermobile Ehlers–Danlos Syndrome: Diagnostic Challenges and the Role of Genetic Testing
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Skewed Lymphocyte Subpopulations and Associated Phenotypes in Patients with Mastocytosis
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Anaphylaxis: Long-term management and resources
Navalpakam, A., Thanaputkaiporn, N., & Poowuttikul, P. (2022) · Allergy and Asthma Proceedings · doi:10.2500/aap.2023.44.220089 · Cited by 7 · see citing works
- Authors
- Lyons, J. J.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Lyons, Jonathan J.
- ORCID
- Lyons, Jonathan J.
- Venue
- Immunology and Allergy Clinics of North America
- Publisher
- Elsevier BV
- Published
- 2018-08
- Volume
- 38
- Issue
- 3
- Pages
- 483-495
- ISSN
- 0889-8561 (ISSN-L)
- PMC
- PMC6411063
- OpenAlex
- W2805441868
- Cited by
- 179
- References
- 40
- Citations by year
- 2026: 23 · 2025: 23 · 2024: 20 · 2023: 23 · 2022: 20 · 2021: 39 · 2020: 15 · 2019: 14 · 2018: 1
- FWCI
- 1.76
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Immunology and Allergy Clinics of North America (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Health Sciences › Medicine › Genetics › Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Keywords
- hereditary alpha-tryptasemia, TPSAB1, autosomal dominant inheritance, gene dosage, serum tryptase, multisystem symptoms
- MeSH terms
- Connective Tissue, Gene Expression Regulation, Genes, Dominant, Genotype, Humans, Hypersensitivity, Immediate, Immunoglobulin E, Mast Cells, Mastocytosis, Skin, Disease Progression, Gene Dosage, Gene Duplication, Quantitative Trait Loci, Tryptases
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