Journal of Allergy and Clinical Immunology Global · Published 2026-05-20 · DOI 10.1016/j.jacig.2026.100737
Daniel Koch, Friederike Wortmann, Andreas Recke, Ellen Rose, Evelyn Gaffal, Jennifer Wigger, Nikolas von Bubnoff, Dagmar von Bubnoff
Background: Hereditary α-tryptasemia (HαT) is a common autosomal-dominant trait caused by additional copies of the gene TPSAB1 encoding for α-tryptase. This inheritance is the most common etiology for elevated basal serum tryptase (BST), occurring almost exclusively at BST ≥ 8 μg/L. In systemic mastocytosis (SM) and nonclonal mast cell–mediated disorders, HαT is linked to a complex constellation of symptoms. Objective: We sought to delineate the spectrum and burden of extended manifestations observed in patients with and without HαT presenting to an allergy department. Methods: A total of 332 allergy patients with BST ≥ 8 μg/L were prospectively enrolled. Blood was tested for HαT and KITD816V mutation (to identify patients with SM) by digital droplet PCR. Symptom assessment was conducted with a HαT-customized questionnaire (n = 256). Results: HαT-positive patients reported a significantly higher symptom burden than HαT-negative patients (9.3 vs 6.5; P < .001), particularly those referred for urticaria/angioedema (8.9 vs 5.5; P = .023) and atopic diseases (8.3 vs 4.2; P = .016). In allergy patients with HαT, symptom spectrum was extended to fatigue (+26%; P < .001), sleep disturbances (+13%; P = .049), and neuropsychiatric symptoms such as concentration issues (+26%; P < .001), memory impairment (+16%; P = .020), sadness/lack of motivation (+22%; P = .004), headaches (+19%; P = .006), abdominal pain (+21%; P = .002), and cardiovascular symptoms such as dizziness (+14%; P = .052), palpitations (+15%; P = .039), and orthostatic dysregulation (+22%; P = .002). Conclusion: HαT may have a broader clinical impact beyond classic allergy–immunology connections and may be associated with extended clinical phenotypes. This suggests an integrative approach to medical practice in allergy patients.
Abstract from DOAJ. Public domain (CC0 1.0).
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Koch, D., Wortmann, F., Recke, A., et al. (2026). Extended multisystem manifestations of hereditary α-tryptasemia in an allergy center cohort. Journal of Allergy and Clinical Immunology Global. https://doi.org/10.1016/j.jacig.2026.100737