D3.343 - Hereditary alpha-tryptasemia: clinical variability and anaphylaxis triggers in six genetically confirmed cases

Hereditary alpha-tryptasemia (HαT) is an autosomal dominant genetic trait caused by increased copy number of the TPSAB1 gene, associated with persistently elevated basal serum tryptase (BST). Although many carriers are asymptomatic, a subset develops immediate hypersensitivity reactions, including anaphylaxis. HαT may also coexist with mast cell disorders.

Retrospective descriptive study of genetically confirmed HαT patients identified at the Allergy Unit of Hospital Universitario de Burgos between January 2024 and January 2026. Clinical, laboratory and genetic variables were analyzed, including anaphylaxis severity (Ring & Messmer), BST levels, mast cell comorbidities and treatment requirements.

Six patients were included (4 males, 2 females), mean age 51 years (range 7–84). Two patients reported a compatible family history. The main reason for evaluation was anaphylaxis (n=5), graded as Ring & Messmer III (n=3) and II (n=2); one patient presented with cutaneous manifestations only. Triggers were foods (n=2), Hymenoptera venom (n=2), medications (n=1, amoxicillin) and physical triggers (n=1). One patient had indolent systemic mastocytosis and another met criteria for mast cell activation syndrome (MCAS); in the remaining cases, high-sensitivity KIT D816V testing was negative. All patients had BST >16 µg/L (mean 21 µg/L; range 17–25.8). TPSAB1 genotypes identified were 3α:2β (n=3) and 2α:3β (n=3). Three patients required on-demand treatment only (antihistamines and/or adrenaline) and three required maintenance therapy (high-dose antihistamines; antihistamines plus sodium cromoglycate; omalizumab).

HαT was associated with a heterogeneous clinical spectrum, frequently manifesting as anaphylaxis with diverse triggers, and occasionally coexisting with mast cell disorders. Persistently elevated basal tryptase should prompt suspicion and genetic confirmation of HαT to optimize diagnostic work-up and refine therapeutic and preventive recommendations.