{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T11:50:27Z","timestamp":1775044227784,"version":"3.50.1"},"reference-count":30,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Background\/Objectives: Hereditary alpha-tryptasemia (H\u03b1T) is increasingly recognized as a genetic modifier of mast cell-mediated disease severity and has been associated with heightened mediator-related symptoms and an elevated risk of anaphylaxis. This study aimed to describe the clinical characteristics, multisystem manifestations, and treatment responses of eight patients with H\u03b1T and concomitant mast cell disorders. Methods: In this single-center retrospective study, eight adults with confirmed TPSAB1 copy number gain and a diagnosis of systemic mastocytosis (SM), cutaneous mastocytosis (CM), or mast cell activation syndrome (MCAS) were evaluated. Baseline assessments included demographics, clinical history, basal serum tryptase (BST), TPSAB1 genotyping, KIT D816V testing, and bone marrow examination when indicated. Symptom burden was quantified at baseline and week 8 using the Mastocytosis Activity Score (MAS). All patients received mediator-targeted therapy; omalizumab was administered in selected high-risk cases. Results: Eight patients (62.5% male, mean age 53.9 \u00b1 12.0 years) carried TPSAB1 duplication. The median BST was 16.2 ng\/mL (range, 14.3\u201351.2). Severe anaphylaxis occurred in 75% of patients, predominantly drug-induced, while Hymenoptera venom triggered the remaining cases. Gastroesophageal reflux (87.5%), cutaneous symptoms (62.5%), neuropsychiatric features (62.5%), and autonomic dysfunction (37.5%) were common. The mean MAS decreased significantly from 27.25 \u00b1 7.40 to 18.25 \u00b1 6.48 after 8 weeks of high-dose antihistamines, with omalizumab providing marked additional benefit in selected patients. Conclusions: In this cohort, patients with H\u03b1T and coexisting mast cell disorders exhibited a high burden of mediator-related symptoms and a notable frequency of anaphylaxis. TPSAB1 genotyping may provide additional genetic information that aids in contextualizing clinical heterogeneity and mediator-related symptom burden in patients with mast cell disorders. Incorporation of H\u03b1T testing into routine evaluation may optimize individualized management.<\/jats:p>","DOI":"10.3390\/jpm16040196","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T10:09:21Z","timestamp":1775038161000},"page":"196","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Emerging Insights into Hereditary Alpha-Tryptasemia in the Context of Mast Cell Disorders: A Greek Case Series"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-0208-9537","authenticated-orcid":false,"given":"Fotios","family":"Koliofotis","sequence":"first","affiliation":[{"name":"National Center of Expertise for Mastocytosis and Mast Cell Disorders, 2nd Department of Dermatology and Venereology, University General Hospital \u201cAttikon\u201d, National and Kapodistrian University of Athens, 12462 Athens, Greece"},{"name":"Allergy Unit, 2nd Department of Dermatology and Venereology, University General Hospital \u201cAttikon\u201d, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8329-6401","authenticated-orcid":false,"given":"Natalia","family":"Katrachoura","sequence":"additional","affiliation":[{"name":"National Center of Expertise for Mastocytosis and Mast Cell Disorders, 2nd Department of Dermatology and Venereology, University General Hospital \u201cAttikon\u201d, National and Kapodistrian University of Athens, 12462 Athens, Greece"},{"name":"Allergy Unit, 2nd Department of Dermatology and Venereology, University General Hospital \u201cAttikon\u201d, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3950-3089","authenticated-orcid":false,"given":"Niki","family":"Papapostolou","sequence":"additional","affiliation":[{"name":"Allergy Unit, 2nd Department of Dermatology and Venereology, University General Hospital \u201cAttikon\u201d, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7607-8005","authenticated-orcid":false,"given":"Styliani","family":"Taka","sequence":"additional","affiliation":[{"name":"Allergy Department, 2nd Pediatric Clinic, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Martinou","sequence":"additional","affiliation":[{"name":"Allergy Department, 2nd Pediatric Clinic, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9234-7073","authenticated-orcid":false,"given":"Anthi","family":"Bouchla","sequence":"additional","affiliation":[{"name":"Hematology Unit, 2nd Propaedeutic Department of Internal Medicine, University General Hospital \u201cAttikon\u201d, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3376-837X","authenticated-orcid":false,"given":"Sotirios G.","family":"Papageorgiou","sequence":"additional","affiliation":[{"name":"National Center of Expertise for Mastocytosis and Mast Cell Disorders, 2nd Department of Dermatology and Venereology, University General Hospital \u201cAttikon\u201d, National and Kapodistrian University of Athens, 12462 Athens, Greece"},{"name":"Hematology Unit, 2nd Propaedeutic Department of Internal Medicine, University General Hospital \u201cAttikon\u201d, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2713-2380","authenticated-orcid":false,"given":"Michael","family":"Makris","sequence":"additional","affiliation":[{"name":"National Center of Expertise for Mastocytosis and Mast Cell Disorders, 2nd Department of Dermatology and Venereology, University General Hospital \u201cAttikon\u201d, National and Kapodistrian University of Athens, 12462 Athens, Greece"},{"name":"Allergy Unit, 2nd Department of Dermatology and Venereology, University General Hospital \u201cAttikon\u201d, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.iac.2018.04.003","article-title":"Hereditary alpha tryptasemia: Genotyping and associated clinical features","volume":"38","author":"Lyons","year":"2018","journal-title":"Immunol. 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