Parent Category: Research
Category: Tryptasemia & Co-Morbidities

PXL 20210131 023717147Every domain has its best (most up-to-date, valuable for patients) literature; for Hereditary Alpha Tryptasemia Syndrome (HATS) they're usually peer-reviewed journal articles, videos from conferences, etc. This annotated bibliography is prioritized in date order; with a newer disorder, having the newest research from the field is critical.

For patient stories, see Faces of Tryptasemia.

2021, DecemberClinical relevance of inherited genetic differences in human tryptases: Hereditary alpha-tryptasemia and beyond

2021, SeptemberSmall intestinal immunopathology and GI-associated antibody formation in hereditary alpha-tryptasemia

2021, AugustRoutine KIT p.D816V screening identifies clonal mast cell disease in patients with Hymenoptera allergy regularly missed using baseline tryptase levels alone. Keywords: Slovenia, KIT-D816V

2021, August 13Clinical relevance of inherited genetic differences in human tryptases: Hereditary alpha-tryptasemia and beyond

2021, August 9Considerations in SM: Hereditary Alpha Tryptasemia. Key words: cancer Mastocytosis 

2021, June 23Hereditary alpha tryptasemia is not associated with specific clinical phenotypes. Key words: Mastocytosis sample size


Elevated baseline serum tryptase was the only consistent phenotypic marker for HαT in this study. There was a higher frequency of HαT in patients with mastocytosis than in the general population.

Note: HATS sample size, n=10; control sample size, n=24. All samples drawn from the University of Michigan or Michigan Genomic Initiative biorepositories.

2021, June 6Hereditary alpha tryptasemia in identical twins. Key words: twins

2021, March 5The genetic basis and clinical impact of hereditary alpha-tryptasemia. Key words: genetics 


There are a number of potential therapeutics in current clinical trials that may hold promise for symptomatic individuals with HaT, including targeting of SIGLEC-8, and IL-33, and even mature tryptase with monoclonal antibodies.

Other potentially valid yet unproven mechanisms that could contribute to symptoms associated with HaT include increased pro-tryptase synthesis and secretion, and/or co-inherited genetic variants.  

2021, FebruaryHeritable risk for severe anaphylaxis associated with increased a-tryptase-encoding germline Copy number at TPSAB1. Key words: Italy US Italy 

Quote: "To our knowledge, this is the first report of a common heritable genetic risk factor for anaphylaxis. Given the increased prevalence of HaT in both severe HVA and IA, the association between HaT and severe anaphylaxis appears to be independent of concomitant clonal mast cell disease."

2021, January 21Distinct Small Intestine Mast Cell Histologic Changes in Patients With Hereditary Alpha-tryptasemia and Mast Cell Activation Syndrome. Key words: small intestine spindle mast cell duodenum mucosa

Screenshot 20210319 18273222021, January 17Hereditary alpha-tryptasemia in 101 patients with mast cell activation-related symptomatology including anaphylaxis. Key words: tryptase >6.2ng/mL omalizumab Xolair™️ psychiatric 👉 A - Baseline; B - Medicated

Quote: "2a:3b was the most common genotype but did not correlate with tryptase levels."

2021, January 14; Hereditary α tryptasemia is a valid genetic biomarker for severe mediator-related symptoms in mastocytosis. Key words: mastocytosis Gdańsk Poland Vienna Austria hymenoptera bee wasp 

2020Mediators of Inflammation in Bone Physiology and Diseases. Key words: hypertryptasemia bone marrow spleen liver gastrointestinal tract University Verona Sheffield Italy United Kingdom


In patients with systemic mastocytosis (SM), neoplastic MCs form focal and/or diffuse infiltrates in various internal organs, including the bone marrow (BM), spleen, liver, and gastrointestinal tract [5]. 

MC-related disorders may be involved in bone fragility and assessment of serum tryptase is useful to detect MC-related disorders.

Recently, a hereditary autosomal dominant form of hypertryptasemia*, caused by increased germline copies of the TPSAB1 gene encoding alpha-tryptase, has been recognized [22–25]. However, genetic analysis could not be performed in the present series of hypertryptasemic patients. [*aka Familial Hypertryptasemia or Hereditary Alpha Tryptasemia Syndrome]

2020, November/DecemberHereditary Alpha Tryptasemia: UK Prevalence and Variability in Disease Expression. Key words: United Kingdom Britain England gene dosage effect not invalidated

Quote: "[C]linical manifestations were not more common in patients with gene triplications or quintuplications than in those with duplications. Some immediate family members with the same genetic trait and high basal MCT levels were asymptomatic." 

2020, NovemberPatients with mast cell activation symptoms and elevated baseline serum tryptase level have unique bone marrow morphology. Key words: bone marrow morphology

2020, November 1The Role of Bone Marrow Evaluation in Clinical Allergy and Immunology Practice: When and Why. Key words: bone marrow

Photo: L. - Dr. Boggs; R - Karen Smith-Will; taken at the NIH.

FB IMG 16172016103512

2020, AprilHereditary Alpha Tryptasemia - New Diagnosis, Familiar Symptoms. Key words: Israel Hebrew

2020, FebruaryYoungest reported child with tryptase >20ug/L, found to have hereditary alpha tryptasemia (HAT). Key words: youngest infant child Canada British Columbia

2020, February 1; Is The Local Anaesthetics a Risk Factor of Anaphylaxis in Mastocytosis Patients? Key words: local anesthesia anesthetic anaphylaxis

2020Elevated Serum Tryptase in Non-Anaphylaxis Cases: A Concise Review. Key Words: Australia hereditary alpha tryptasemia familial hypertryptasemia ImmunoCAP enzyme-linked immunosorbent assay ELISA

Quote: "MCs from these patients do not appear to be more prone to degranulation, indicating the problem is not a disorder of MC activation."

2019, DecemberMast cell activation in the context of elevated basal serum tryptase: genetics & presentations. Key Words: gene dosage effect germline quintuplication

Quote: "One additional TPSAB1 copy results in an averageBST level of 15 ± 5 ng/mL, two extra copies 24 ± 6 ng/mL, and in the family with four extra copies 37 ± 14 ng/mL."

2019, NovemberComplex, persistent, multi-generational Presentation of Hereditary Alpha Tryptasemia Syndrome requiring high dose omalizumab. Key words: 

2019, AugustLipidomic analysis of urinary exosomes from hereditary α‐tryptasemia patients and healthy volunteers. Key words: lipids urine urinary upregulation exosomes secretion lipidome University Florida

2019 Special edition The Mast Cell Society Newsletter Search for: TMS_Chronicles_SE_2019_v1.pdf Key words: Mast Cell stabilizers medications supplements H1s H2s tables

2018; A case of Hereditary Alpha Tryptasemia successfully treated with omalizumab. Key words: omalizumab Xolair™️ preadolescent triplication pre-teen

2017, AugustA common haplotype containing functional CACNA1H variants is frequently coinherited with increased TPSAB1 copy number. Key words: CACNA1H 
2015Alpha tryptase allele of Tryptase 1 (TPSAB1) gene associated with Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) in Vietnam and Philippines. Key words: TPSAB1 Dengue FeverPhilippines Vietnam

2014, OctoberMastocytic Enterocolitis as a Rare Cause of Chronic Diarrhea. Key words: high-powered field hpf CD117 staining diarrhea

Quote: "Mastocytic enterocolitis is a rare, recently defined disorder characterized by an increased number of gut diarrheast cells (>20 per high power field [or, hpf]) that are revealed by immunohistochemical demonstration of mast cell tryptase in patients with chronic diarrhea. This disorder can be easily missed if immunohistochemical staining for mast cells is not done."

2014, July 30Familial hypertryptasemia with associated mast cell activation system. Key words: Antwerp Belgium

2014, January 25Mendelian inheritance of elevated serum tryptase associated with atopy and connective tissue abnormalities. Key words: NIH University Cincinnati Virginia Commonwealth

Quote: "Additional genetic study is ongoing, and as the dysfunctional pathways in these families are elucidated, we might gainvadditional insights into the hypermobile connective tissue phenotype, atopic disease, autonomic dysfunction, and neuropsychiatric illness and their interface with mast cell mediators."

2012, MarchAllergic Mastocytic Gastroenteritis and Colitis: An Unexplained Etiology in Chronic Abdominal Pain and Gastrointestinal Dysmotility. Key words: CD117 staining mastocytic enterocolitis gastrointestinal gastroenterology high-powered field HPF

Quote: "Solid gastric emptying was increased as were the mean number of mast cells reported on biopsies from the stomach, small bowel, and colon (>37/hpf) by CD117 staining...This study suggests that in individuals with these characteristics, consideration should be given to staining their gastrointestinal biopsies for mast cells as this may provide them with relatively non-toxic but highly targeted treatment options. Allergic gastroenteritis and colitis may represent a third type of GI mast cell disorder along with mast cell activation syndrome and mastocytic enterocolitis."

2012FDA clears test developed in partnership with VCU researcher. Key words: ImmunoCAP Assay Test Virginia Commonwealth University


Additional Key words for Annotated Bibliography:

White Papers Peer-reviewed Medical Journals



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