Hereditary α-tryptasemia (HαT) is a common autosomal dominant genetic trait with variable penetrance associated with increased serum baseline tryptase (SBT) levels. Clinical manifestations may range from an absence of symptoms to overtly severe and recurrent anaphylaxis. Symptoms have been claimed to result from excessive activation of EGF-like module-containing mucin-like hormone receptor-like 2 (EMR2) and protease-activated receptor 2 (PAR-2) receptors by α/β-tryptase heterotetramers. Herein, we aimed to review the evidence on whether HαT can be considered a hereditary risk factor or a modifying factor for anaphylaxis.Increased SBT levels have been linked to an increased risk of anaphylaxis. Likewise, recent studies have shown that HαT might be associated with a higher risk of developing anaphylaxis and more severe anaphylaxis. The same has also been shown for patients with clonal mast cell disorders, in whom the co-existence of HαT might lead to a greater propensity for severe, potentially life-threatening anaphylaxis. However, studies leading to such conclusions are generally limited in sample size, while other studies have shown opposing results. As such, further studies investigating the potential association of HαT with anaphylaxis caused by different triggers, and different severity grades, in both patients with clonal mast cell activation syndromes and the general population are still needed.
Keywords: Anaphylaxis; hereditary alpha-tryptasemia syndrome; mast cell activation syndrome; serum baseline tryptase; tryptase.