Hereditary alpha-tryptasemia (HαT) is an autosomal dominant genetic trait characterized by an increased copy number of the TPSAB1 gene, which encodes alpha-tryptase. This condition leads to elevated serum basal tryptase (sBT) levels and has emerged as a critical genetic modifier of anaphylaxis severity. Clinical expression is highly heterogeneous, ranging from asymptomatic individuals to complex multisystemic phenotypes. The aim of this study is to describe the clinical and laboratory characteristics of patients diagnosed with HαT in our Allergy Department.

 A retrospective descriptive study was conducted on six patients diagnosed with HαT at the Allergy Department of the San Cecilio University Clinical Hospital in Granada between 2022 and 2025. The diagnosis was suspected in the presence of persistent sBT levels >8 ng/mL and confirmed by digital PCR (dPCR). Demographic data, clinical manifestations, comorbidities, and laboratory findings were analyzed.

The study sample  included a total of six patients (one female and five males), with a mean age of 54 years (range: 45–65). All patients had experienced more than one episode of anaphylaxis. Identified triggers included the ingestion of rosaceae fruits and tree nuts (1), crustaceans (1), administration of non-steroidal anti-inflammatory drugs (2), and hymenoptera stings (1). During these episodes, all patients exhibited cutaneous symptoms (flushing, urticaria, or angioedema); additionally, five patients presented with gastrointestinal symptoms (diarrhea, abdominal pain), and four experienced dysautonomic symptoms (tachycardia, hypotension, syncope). Neuropsychiatric, constitutional, or joint hypermobility symptoms, as described in other case series, were not observed.

The mean sBT level was 17.77 ng/mL (median: 15.2; range: 11.8–29.2). Genetic testing revealed an increased copy number of α-tryptase encoded by the TPSAB1 gene in all cases. Three patients were concomitantly diagnosed with non-clonal Mast Cell Activation Syndrome.

In our case series, HαT manifests as severe anaphylactic episodes with a predominance of gastrointestinal symptoms and autonomic dysfunction. These findings underscore the importance of performing HαT screening in patients with elevated basal serum tryptase or recurrent anaphylaxis without an identifiable trigger. The identification of this genetic trait is essential for risk stratification and the optimization of patient management.