Hereditary alpha-tryptasemia - a potential cause of severe anaphylactic reactions and a modifier of mast cell diseases.

Hereditary alpha-tryptasemia (HAT) is an autosomal dominant genetic trait affecting 4% to 6% of the general population. Hereditary alpha-tryptasemia is caused by an excess of alpha tryptase encoding TPSAB1 copy numbers on one parenteral allele, most often duplications or triplications, leading to elevated levels of basal serum tryptase. There might be a gene dosage effect between the number of additional TPSAB1 copies, the level of basal serum tryptase and the severity of clinical symptoms, including atopic, cutaneous, gastrointestinal, musculoskeletal, autonomic and neuropsychiatric manifestations. Hereditary alpha-tryptasemia is a potential risk factor for severe anaphylactic reactions. The prevalence of hereditary alpha-tryptasemia is higher in patients with systemic mastocytosis. In the diagnostic workup of patients with anaphylactic reactions and symptoms of mast cell mediator release after measurement of basal serum tryptase, it is therefore essential to screen for both the KIT D816V activating point mutation and hereditary alpha-tryptasemia by droplet digital polymerase chain reaction. Such a diagnostic approach can identify patients with hereditary alpha-tryptasemia, which may allow the avoidance of further diagnostic workup with bone marrow examination. Moreover, it can identify patients at high risk of anaphylactic reactions. So far, no targeted therapy for hereditary alpha-tryptasemia is available. Treatment for symptom control consists of H1- and H2-blockers, leukotriene antagonists and cromoglicic acid. Urticaria and anaphylaxis are especially successfully treated with the monoclonal anti-IgE-antibody omalizumab in patients with hereditary alpha-tryptasemia. H1-blockers and steroids are sufficient in emergencies. As hereditary alpha-tryptasemia is a hereditary condition, first-degree relatives with anaphylactic reactions or symptoms of mast cell mediator release should be tested for hereditary alpha-tryptasemia after measurement of basal serum tryptase.