Hereditary α-Tryptasemia and Peripheral Blood D816V Mutation in Patients with Pediatric Mastocytosis.

Hereditary α-tryptasemia (HαT)-a genetic trait caused by increased α-tryptase-encoding typtase alpha/beta-1 (TPSAB1) copy number-is associated with adult mastocytosis. The primary objective was to assess the association between α-tryptase and pediatric mastocytosis. We also want to evaluate whether the p.D816V mutation in peripheral blood leukocytes (PBLs) reliably predicts systemic mastocytosis (SM) in children. A prospective cohort of 68 children from a referral center in Slovenia with cutaneous mastocytosis (CM) underwent tryptase genotyping by droplet digital PCR and examination for p.D816V in PBL using a sensitive PCR test. A significant majority of patients (57 of 68; [83.8%]) had at least one α-tryptase-encoding gene; none had HαT. 7 of the 68 (10.3%) who were positive for p.D816V in PBL, one fulfilled diagnostic criteria for indolent SM, and another was diagnosed with monoclonal mast cell activation syndrome. One of those individuals had an increased basal serum tryptase (BST) level (14.5 ng/mL). We found a high presence of germline α-tryptase in children with CM, but not HαT. By employing sensitive examination for p.D816V in PBL, in combination with clinical data and other examinations, our study suggests that p.D816V in PBL may indicate systemic disease in children with CM.