Intra familial expression of Alpha tryptasemia

Hereditary alpha- tryptasemia (HαT) is a common genetic disorder resulting from an increased copy number of the TPSAB1 gene that causes persistently elevated basal serum tryptase levels. HαT presents with a broad and heterogeneous clinical spectrum. Although not a disease per se, HαT may act as an amplifying factor in various clinical contexts, particularly in disorders involving mast cell reactivity. We report two cases - mother and daughter - with identical TPSAB1 duplications, but with markedly different clinical profiles. The mother developed moderate symptoms of episodic pruritus, urticaria, and exertional dyspnea that responded to antihistamines and a low-histamine diet. In contrast, the daughter presented with early-onset and persistent symptoms, including angioedema, urticaria, bronchial obstruction, and dysmenorrhea. Neither patient showed evidence of IgE-mediated allergy, systemic inflammation or eosinophilia, and systemic mastocytosis was excluded (absence of cKIT mutation). These observations underscore the symptomatic variability of HαT and highlight the phenotypic heterogeneity of this genetic disorder even within the same family.