About this condition
Hereditary Alpha Tryptasemia — HαT
Hereditary alpha tryptasemia (HαT) is caused by increased copy number of the TPSAB1 gene (chromosome 16p13.3), encoding alpha-tryptase. HαT is extraordinarily common — affecting approximately 5-8% of the general population — yet is almost never diagnosed because TPSAB1 copy number testing is not performed in routine clinical practice. Individuals with HαT have elevated baseline serum tryptase levels (typically 8-30 ng/mL vs. normal <11.4).
HαT is associated with: (1) more severe anaphylaxis and IgE-mediated allergic reactions, (2) dysautonomia and POTS symptoms, (3) GI dysmotility (functional dyspepsia, IBS-like symptoms), (4) flushing episodes, (5) skin findings (dermatographia), and (6) skeletal abnormalities (retained primary teeth, fifth finger clinodactyly). HαT is significantly enriched in patients diagnosed with mast cell activation syndrome (MCAS) and may explain many MCAS cases.
Identification of HαT has direct therapeutic implications: mast cell-directed therapy (H1/H2 antihistamines, cromolyn sodium, ketotifen) targets the underlying elevated tryptase and mast cell mediator release. Omalizumab (anti-IgE) may be particularly effective for HαT with allergic manifestations. Additionally, HαT patients requiring procedures with anaphylaxis risk benefit from premedication protocols. Without HαT diagnosis, these patients receive empirical symptom management rather than mechanism-directed therapy.
5-8% of people have HαT — it's one of the most common genetic conditions. Yet it's almost never tested for. If you have unexplained anaphylaxis, flushing, GI dysmotility, or POTS, HαT may be the answer.
- Gene locus
- TPSAB1 (16p13.3)
