Every 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.

2024, January 6; A clinical, morphological and molecular study of 70 patients with gastrointestinal involvement in systemic mastocytosis Keywords: Heidelberg Germany gastrointestinal

2023, July 23;  Re-educating mast cells Keywords: immunology, hypermobility, Ehlers-Danlos, CD117 staining

• Maitland, Anne. Video conference hosted by New York Medical College via Zoom, "9th East West integrative medical symposium for immunology and wellness"

2023, May 9; Genetically defined individual reference ranges for tryptase limit unnecessary procedures and unmask myeloid neoplasms Keywords: bone marrow biopsy, systematic mastocytosis, indolent systematic mastocytosis, urticaria, hyperplasia, monoclonal mast cell activation

• Jack Chovanec, Ilker Tunc, Jason Hughes, Joseph Halstead, Allyson Mateja, Yihui Liu, Michael P. O’Connell, Jiwon Kim, Young Hwan Park, Qinlu Wang, Quang Le, Mehdi Pirooznia, Neil N. Trivedi, Yun Bai, Yuzhi Yin, Amy P. Hsu, Joshua McElwee, Sheryce Lassiter, Celeste Nelson, Judy Bandoh, Thomas DiMaggio, Julij Å elb, Matija Rijavec, Melody C. Carter, Hirsh D. Komarow, Vito Sabato, Joshua Steinberg, Kurt M. Hafer, Elizabeth Feuille, Christopher S. Hourigan, Justin Lack, Paneez Khoury, Irina Maric, Roberta Zanotti, Patrizia Bonadonna, Lawrence B. Schwartz, Joshua D. Milner, Sarah C. Glover, Didier G. Ebo, Peter KoroÅ¡ec, George H. Caughey, Erica H. Brittain, Ben Busby, Dean D. Metcalfe, Jonathan J. Lyons,
• Blood Advances, Volume 7, Issue 9, 2023, Pages 1796-1810

2023, April 14;  The Curious Case of Elevated Tryptase: Workup and Differential in Family of Four Keywords: Chronic urticaria, episodic facial angioedema

• Audra L. Cochran, Christopher Coop, Brittanie I. Neaves, Stuart T. Wood. Published: April 24, 2023 (see history)
• DOI: 10.7759/cureus.38065
• Keesler Medical Center, Biloxi, Mississippi 
• "This case series is unique in that all members of the family with elevated BST were symptomatic, which would be a relatively unusual presentation of HaT." 
• Webmaster/Author's Note: It is unclear why the authors considered this a "relatively unusual presentation", given the existence of multiple similar family units in the Mayo Clinic and NIH cohorts, with a similar proliferation of features. Nonetheless, it is favorable to have another HATS paper published, as well as an additional medical facility with interest in HATS.

2023, January 18; Clonal mast cell disorders and hereditary α-tryptasemia as risk factors for anaphylaxis Keywords: Ljubljana Slovenia anaphylaxis 

• XMark Kačar, Matija Rijavec, Julij Šelb, Peter Korošec; early access
• University of Ljubljana, Ljubljana, Slovenia
• "Since its discovery, HαT has been found in 3–5.5% of the general population, with a moderate female preponderance of 64%."
• Notable for its "Suggested formulae and clinical calculator for determining TPSAB1 copy number-normalized tryptase levels." ⤵️

2022, December 30; Evaluating the Differential Mast Cell Mediators in HαT and Systemic Mastocytosis. Keywords: urinary 

• Physicians Weekly; Originally published published in the November 2022 issue of Allergy and Clinical Immunology by Giannetti, et al. jacionline.org/article/S0091-6749(22)00621-2/fulltext
• Note that this is an article already posted a couple of times below. What's important here, is that HATS is being highlighted in a higher-level, generalized periodical.

2022, August 13; Outcomes of COVID-19 vaccination in 323 patients with clonal and non-clonal mast cell activation disorders. Keywords: COVID

• Matthew P. Giannetti,Francesco Olivieri,Grace Godwin,Emma Weller,Jennifer Nicoloro-SantaBarbara,Patrizia Bonadonna,Roberta Zanotti,Giovanna Zanoni,Karin Hartmann,Mariana Castells
  First published: 13 August 2022
  https://doi.org/10.1111/all.15476

2022, May 8; Differential mast cell mediators in systemic mastocytosis and hereditary α-tryptasemia. Keywords: urinary N-methylhistamine ISM Hospital Mastocytosis Center Mayo Clinic

• J Allergy Clin Immune. Matthew P. Giannetti, MD  ∗
  Grace Godwin, BA ∗ Emily Weller, BA Joseph H. Butterfield, MD Mariana Castells, MD, PhD Published:May 08, 2022DOI: https://doi.org/10.1016/j.jaci.2022.04.025

Quote:

"Patients with symptomatic HαT do not have elevations of mast cell urinary metabolites, suggesting that granule- and membrane-derived mediators may not drive symptoms in HαT."

2021, December 18; Adult-onset mast cell activation syndrome following scombroid poisoning: a case report and review of the literature

Keywords: scombroid, poisoning, hyper alpha tryptasemia, MCAS, immunology, hypermobility

• J Med Case Rep. 2021; 15: 620. Published online 2021 Dec 18. doi: 10.1186/s13256-021-03190-w
• Isabelle Brock, Nicole Eng & Anne Maitland

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

• Xx

2021, September; Small intestinal immunopathology and GI-associated antibody formation in hereditary alpha-tryptasemia

• J Allergy Clin Immun. 2021 Sep; 148(3):813-821.e7doi: 10.1016/j.jaci.2021.04.004.Epub 2021 Apr 15. Liza Konnikova1, Tanya O Robinson2, Anna H Owings2, James F Shirley3, Elisabeth Davis4, Ying Tang5, Sarah Wall6, Jian Li3, Mohammad H Hasan2, Raad Z Gharaibeh3, Lybil B Mendoza Alvarez7, Lisa K Ryan8, Andria Doty9, Jack F Chovanec10, Michael P O'Connell10, Dianne E Grunes11, William P Daley11, Emeran Mayer12, Lin Chang12, Julia Liu13, Scott B Snapper6, Joshua D Milner14, Sarah C. GloverThis email address is being protected from spambots. You need JavaScript enabled to view it..">15, Jonathan J LyonsThis email address is being protected from spambots. You need JavaScript enabled to view it..">16

2021, August; Routine 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

• Journal of Allergy and Clinical Immunology, Vol. 148, Issue 2, August 2021, Pages 621-626.e7 Routine KIT p.D816V screening identifies clonal mast cell disease in patients with Hymenoptera allergy regularly missed using baseline tryptase levels alone
  JulijŠelbMD, PhDab∗MatijaRijavecPhDac∗RenatoErženMD, PhD, MihaelaZidarnMD, PhDab, PeterKopačMDabMatevžŠkergetMD, PhDbdNisseraBajrovićMDab, Ajda DemšarLuzarMScaYoung HwanParkPhD, eYihuiLiuPhDeVladka ČurinŠerbecPhD, fSamoZverMD, PhDbdMitjaKošnikMD, PhDab, Jonathan J.LyonsMD, PeterKorošecPhDa

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

• Ann Allergy Asthma Immunoloy, 2021 Aug 13; S1081-1206(21)00567-6. doi: 10.1016/j.anai.2021.08.009.Online ahead of print; Sarah C Glover1, Melody C Carter2, Peter Korošec3, Patrizia Bonadonna4, Lawrence B Schwartz5, Joshua D Milner6, George H Caughey7, Dean D Metcalfe2, Jonathan J LyonsThis email address is being protected from spambots. You need JavaScript enabled to view it..">

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

• Daniel J. DeAngelo, MD, PhD, Dana-Farber Cancer Institute, Sa Wang, MD, MD Anderson Cancer Center, Prithviraj Bose, MD, MD Anderson Cancer Center, Patricia Lugar, MD, MS, Duke Health. Systematic mastercytosis: episode 3. Onc live, 2021.

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

• Madeleine B.CholletMD, PhDCemAkinMD, PhD, Division of Allergy, University of Michigan, Ann Arbor. Received 1 February 2021, Revised 12 May 2021, Accepted 16 June 2021, Available online 23 June 2021

Quote: 

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 6; Hereditary alpha tryptasemia in identical twins. Key words: twins

• Louise H. Bethea, Karen S. Tuano, Neha Seth, Javier Chinen, Hereditary alpha tryptasemia in identical twins,
  Annals of Allergy, Asthma & Immunology, Volume 127, Issue 4, 2021, Pages 503-504, ISSN 1081-1206,
  https://doi.org/10.1016/j.anai.2021.06.011.
  (https://www.sciencedirect.com/science/article/pii/S108112062100449X)

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

• Kathleen T. Luskin, Andrew A. White, Jonathan J. Lyons, The genetic basis and clinical impact of hereditary alpha-tryptasemia, The Journal of Allergy and Clinical Immunology: In Practice, 2021, ISSN 2213-2198,
  https://doi.org/10.1016/j.jaip.2021.03.005.
  (https://www.sciencedirect.com/science/article/pii/S2213219821003068)

Quotes:

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, February; Heritable 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."

• Lyons JJ, Chovanec J, O'Connell MP, Liu Y, Šelb J, Zanotti R, Bai Y, Kim J, Le QT, DiMaggio T, Schwartz LB, Komarow HD, Rijavec M, Carter MC, Milner JD, Bonadonna P, Metcalfe DD, Korošec P. Heritable risk for severe anaphylaxis associated with increased α-tryptase-encoding germline copy number at TPSAB1. J Allergy Clin Immunol. 2021 Feb;147(2):622-632. doi: 10.1016/j.jaci.2020.06.035. Epub 2020 Jul 24. PMID: 32717252.

2021, January 21; Distinct 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

• Hamilton, Matthew J. MD*; Zhao, Melissa MD†; Giannetti, Matthew P. MD‡; Weller, Emily BA‡; Hufdhi, Raied MD‡; Novak, Peter MD§; Mendoza-Alvarez, Lybil B. MD∥; Hornick, Jason MD, PhD†; Lyons, Jonathan J. MD¶; Glover, Sarah C. DO#,**; Castells, Mariana C. MD, PhD‡; Pozdnyakova, Olga MD, PhD†Author Information
  The American Journal of Surgical Pathology: January 20, 2021 - Volume Publish Ahead of Print - Issue -
  doi: 10.1097/PAS.0000000000001676

2021, January 17; Hereditary 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."

• Matthew P. Giannetti, Emily Weller, Concetta Bormans, Peter Novak, Matthew J. Hamilton, Mariana Castells, Hereditary alpha-tryptasemia in 101 patients with mast cell activation-related symptomatology including anaphylaxis, Annals of Allergy, Asthma & Immunology, 2021, ISSN 1081-1206, https://doi.org/10.1016/j.anai.2021.01.016.(http://www.sciencedirect.com/science/article/pii/S1081120621000247)

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 

• Blood (2021) 137(2): 238-137.

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

Quotes:

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]

• Giulia Carosi, Gregorio Guabello, Matteo Longhi, Federica Grifoni, Elena Passeri, Sabrina Corbetta, "Hypertryptasemia and Mast Cell-Related Disorders in Severe Osteoporotic Patients", Mediators of Inflammation, vol. 2020, Article ID 5785378, 8 pages, 2020. https://doi.org/10.1155/2020/5785378

2020, November/December; Hereditary 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." 

• Robey RC, Wilcock A, Bonin H, Beaman G, Myers B, Grattan C, Briggs TA, Arkwright PD. Hereditary Alpha-Tryptasemia: UK Prevalence and Variability in Disease Expression. J Allergy Clin Immunol Pract. 2020 Nov-Dec;8(10):3549-3556. doi: 10.1016/j.jaip.2020.05.057. Epub 2020 Jun 15. PMID: 32553831.

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

• Giannetti MP, Akin C, Hufdhi R, Hamilton MJ, Weller E, van Anrooij B, Lyons JJ, Hornick JL, Pinkus G, Castells M, Pozdnyakova O. Patients with mast cell activation symptoms and elevated baseline serum tryptase level have unique bone marrow morphology. J Allergy Clin Immunol. 2020 Nov 25:S0091-6749(20)31633-X. doi: 10.1016/j.jaci.2020.11.017. Epub ahead of print. PMIDNo: 33248113.

2020, November 1; The 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.

• REVIEW AND FEATURE ARTICLE| Vol. 8, Iss. 10, P3356-3362, NOVEMBER 01, 2020
  The Role of Bone Marrow Evaluation in Clinical Allergy and Immunology Practice: When and Why
  Nathan A. Boggs, MD, PhD& V. Koneti Rao, MD Published:June 08, 2020 DOI:https://doi.org/10.1016/j.jaip.2020.05.049

2020, April; Hereditary Alpha Tryptasemia - New Diagnosis, Familiar Symptoms. Key words: Israel Hebrew

• Cohen Engler A, Confino Cohen R, Mekori Y. Hereditary Alpha Tryptasemia - New Diagnosis, Familiae Symptoms. Harefuah. 2020 Apr;159(4):253-255. Hebrew. PMID: 32307961.

2020, February; Youngest 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

2020; Elevated 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."

• https://www.karger.com/Article/FullText/506199#ref29

2019, December; Mast 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, November; Complex, persistent, multi-generational Presentation of Hereditary Alpha Tryptasemia Syndrome requiring high dose omalizumab. Key words: 

• M. Paul, D. Engler, M159 COMPLEX, PERSISTENT, MULTI-GENERATIONAL PRESENTATION OF HEREDITARY ALPHA TRYPTASEMIA SYNDROME REQUIRING HIGH DOSE OMALIZUMAB, Annals of Allergy, Asthma & Immunology, Volume 123, Issue 5, Supplement, 2019, Page S90, ISSN 1081-1206, https://doi.org/10.1016/j.anai.2019.08.159 (https://www.sciencedirect.com/science/article/pii/S1081120619307483)

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

• Glover SC, Nouri M‐Z, TunaKM, et al. Lipidomic analysis of urinary exosomes from hereditary α‐tryptasemian patients and healthy volunteers. FASEB BioAdvances. 2019;1:624–638. https ://doi.org/10.1096/fba.2019-00030

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

• J.J. Rosenthal, C. Swanson, D. Petroni, A case report of Hereditary Alpha Tryptasemia successfully treated with omalizumab, Annals of Allergy, Asthma & Immunology, Volume 121, Issue 5, Supplement, 2018, Page S122, ISSN 1081-1206, https://doi.org/10.1016/j.anai.2018.09.405.(http://www.sciencedirect.com/science/article/pii/S1081120618311517)

• Lyons, Jonathan & Stotz, Stephanie & Chovanec, Jack & Liu, Yihui & Lewis, Katie & Nelson, Celeste & Dimaggio, Thomas & Jones, Nina & Stone, Kelly & Sung, Heejong & Biesecker, Leslie & Colicos, Michael & Milner, Joshua. (2017). A common haplotype containing functional CACNA1H variants is frequently coinherited with increased TPSAB1 copy number. Genetics in Medicine. 20. 10.1038/gim.2017.136.

• Velasquez CV, Roman AD, Lan NT, Huy NT, Mercado ES, Espino FE, Perez ML, Huong VT, Thuy TT, Tham VD, Nga CT, Ha TT, Bilar JM, Bajaro JD, Baello BQ, Kikuchi M, Yasunami M, Morita K, Watanabe N, Karbwang J, Hirayama K. Alpha tryptase allele of Tryptase 1 (TPSAB1) gene associated with Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) in Vietnam and Philippines. Hum Immunol. 2015 May;76(5):318-23. doi: 10.1016/j.humimm.2015.03.009. Epub 2015 Mar 20. PMID: 25797204.

2014, October; Mastocytic 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."

• Abdinoor, Abdillahi MD; Venu, Mukund MD, American Journal of Gastroenterology: October 2014 - Volume 109 - Issue - p S428.

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

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

• Lyons J.J., Sun G., Stone K.D., Nelson C., Wisch L., O'Brien M., et al. Mendelian inheritance of elevated serum tryptase associated with atopy and connective tissue abnormalities. J Allergy Clin Immunol. 2014; 133: 1471-1474. Available online January 25, 2014. http://dx.doi.org/10.1016/j.jaci.2013.11.039

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, March; Allergic 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

• March 2012, Gastroenterology Research and Practice 2012(4):950582. DOI: 10.1155/2012/950582. SourcePubMed; LicenseCC BY 3.0A. Akhavein M, N.R. Patel, Pravin Muniyappa, Sarah Glover

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."

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

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Additional Key words for Annotated Bibliography:

White Papers Peer-reviewed Medical Journals

 

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