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. 2025 Jun 23;26(13):6023.
doi: 10.3390/ijms26136023.

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

Olga Tockova  1 , Tanja Planinsek Rucigaj  1 , Simona Ivancan  2 , Urska Bidovec Stojkovic  3 , Matija Rijavec  3   4 , Julij Šelb  3 , Peter Korošec  3   5
Affiliations

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

Olga Tockova et al. Int J Mol Sci. .

Abstract

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 KIT 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 KIT 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 KIT 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 KIT p.D816V in PBL, in combination with clinical data and other examinations, our study suggests that KIT p.D816V in PBL may indicate systemic disease in children with CM.

Keywords: KIT D816V; bone marrow; diagnosis; hereditary α-tryptasemia; mastocytosis; pediatrics; peripheral blood.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
(A) The distribution of tryptase genotypes and (B) the prevalence of carriers with α-tryptase in patients with pediatric mastocytosis. (C) The relationship between BST levels and the presence of KIT p.D816V. The data are presented as boxes and whiskers. The horizontal line within the box represents the median and the box represents the 25th to 75th percentile. The whiskers represent the ranges. KIT p.D816V+ patients are represented by red dots and KIT p.D816V− by grey dots. Mann–Whitney test was used for calculation. BST: basal serum tryptase.
Figure 2
Figure 2
The relationship between BST levels and tryptase genotype. The data are presented as boxes and whiskers. The horizontal line within the box represents the median and the box represents the 25th to 75th percentile. The whiskers represent the ranges. Kruskal–Wallis test followed by Dunn’s post hoc test was used for calculation. BST: basal serum tryptase.
Figure 3
Figure 3
Mastocytosis subtypes according to the presence of the KIT p.D816V mutation in peripheral blood leukocytes, α-tryptase-encoding gene, and bone marrow studies.
See this image and copyright information in PMC

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