Incorporating Tryptase Genotyping Into the Workup and Diagnosis of Mast Cell Diseases and Reactions

The measurement of mast cell tryptase levels in serum has found utility in the diagnosis and management of both clonal mast cell disorders and severe mast cell-dependent systemic reactions in the form of anaphylaxis. A more recent discovery is that a majority of individuals with elevated basal serum tryptase levels have increased germline TPSAB1 gene copy number encoding α-tryptase. This genetic trait is referred to as hereditary α-tryptasemia (HαT) and affects nearly 6% of the general population. In clinical practice, the presence or absence of HαT should thus now be determined when defining what constitutes an abnormal serum tryptase level in the diagnosis of mastocytosis. Further, as rises in serum tryptase levels are used to support the diagnosis of systemic anaphylaxis, variability in baseline serum tryptase levels should be factored into how significant a rise in serum tryptase is required to confirm the diagnosis of a systemic allergic reaction. In practicality, this dictates that symptomatic individuals undergoing evaluation for a mast cell-associated disorder or reaction with a baseline serum tryptase level exceeding 6.5 ng/mL should be considered for tryptase genotyping in order to screen for HαT. This review provides detailed information on how to use the results of such testing in the diagnosis and management of both mastocytosis and anaphylaxis.