Editorial: Hereditary alpha-tryptasemia: 10 years on

Hereditary alpha-tryptasemia (HαT) has emerged over the past decade as an important genetic modifier of mast cell-mediated disease and anaphylaxis. First described in 2016 by Lyons and colleagues, HαT is an autosomal dominant genetic trait caused by increased germline copy numbers of the TPSAB1 gene encoding α-tryptase. It affects approximately 4%-6% of Western populations and is now recognized as the most common cause of elevated basal serum tryptase (BST) levels in otherwise healthy individuals. Despite its high prevalence, the clinical penetrance of HαT is remarkably heterogeneous. Approximately one-third of individuals carrying the trait remain asymptomatic, whereas others develop multisystem manifestations that include flushing, pruritus, gastrointestinal symptoms, and recurrent systemic reactions. While associations with connective tissue abnormalities, dysautonomia, joint hypermobility, and postural orthostatic tachycardia syndrome (POTS) were initially reported, these were later disproven. Importantly, HαT is best understood as a genetic trait rather than a disease entity, with clinical relevance that depends strongly on context.