Incidence: very rare but probably unknown and not recognized, and therefore undiagnosed. Autosomal dominant transmission of a mutation   resulting in an increased number of copies of the TPSAB1 gene (16p13.3) coding for alpha-tryptase. It codes either for beta-tryptase (also known as "β-tryptase" or "tryptase beta" or "beta-1 tryptase"), or alpha-tryptase or "alpha-1 tryptase".

This gene frequently presents with a variable number of copies but 20 % of the population (45 % of Caucasians) does not express this gene at all and has no symptoms. The 4 genes that code for tryptase (TPSG1, TPSB2, TPSAB1 and TPSD1) are located on the same locus. Tryptases are serum proteases expressed in basophils and mast cells. Pro-tryptases are secreted in the basal state in mast cells and tryptase is stored in mast cell granules and basophils from which it is released by activated cells. Tryptase is active in its tetrameric form and its allosteric form varies according to the monomers from which it is formed: e.g., 4-alpha tetramers have no protease activity.

The increased number of copies of the TPSAB1 gene, by duplication, triplication or quintuplation results in an elevated basal serum tryptase levels and could explain some cases of mast cell activation syndrome (see this term). It is also found in some cases of mastocytosis (see this term).

The clinical expression is variable: there is a correlation between the number of additional TPSAB1 copies, the basal serum tryptase levels and the symptoms severity. The higher the TPSAB1 copy number, the higher the basal serum tryptase level, and the severity of symptoms.

These include:

-        few or no symptoms

-        cutaneous signs: recurrent urticaria, skin rash, angioedema

-        gastrointestinal signs: abdominal pain, diarrhea, food intolerances

-        systemic signs: allergic or anaphylactic reactions, especially in case of hymenoptera bite

-        dysautonomic signs: hypotension or orthostatic tachycardia

-        sleep disorders, chronic pain, joint hyperlaxity

Treatment: antihistaminics, autoinjectable epinephrine

Anesthetic implications:

increased risk of anaphylactic reaction; although no cases of anesthetic management have been described, it is wise to apply the same recommendations as in case of mastocytosis (see this term).

References :

-        Zama D, Muratore E, Giannetti A, Neri I, Conti F, Magini P, Ferrari S, Pession A.
Case report : hereditary alpha tryptasemia in children : a pediatric case series and a brief overview of literature.
Front Pediatr 2021 ; 9 : 716786

Updated: May 2024