Biological diagnosis of hereditary alpha-tryptasemia

Abstract

Hereditary alpha-Tryptasemia (HαT) is the most frequent of TPSAB1/TPSB2 copy number variations. It is present in up to 6% of the general population and is associated with higher basal serum tryptase (bST) levels. HαT is considered a modifier of the frequency and severity of anaphylaxis in patients with clonal Mast Cell Disorders (MCD) or IgE-mediated allergy, particularly in venom-triggered or idiopathic anaphylaxis. Tryptase genotyping is adequately performed using droplet digital PCR (ddPCR), by comparing apparent copy numbers of α-tryptase, β-tryptase alleles and a housekeeping gene in digested and non-digested conditions. This method allows genotype resolution in most individuals. Tryptase genotyping is indicated in all symptomatic individuals with anaphylaxis history and/or Mast Cell Activation Syndrome (MCAS) suspicion and bST ≥8μg/L, in order to confirm or exclude HαT as an explanation of tryptase levels. In addition, tryptase genotyping is recommended for classification and risk-stratification of MCAS. Finally, in systemic mastocytosis, HαT status modifies the bST thresholds used for diagnostic, classification and risk-stratification purposes. Asymptomatic subjects or individuals with bST<6μg/L should not undergo tryptase genotyping, unless required for genotype resolution of related symptomatic individuals.