D1.291 - Hypertryptasemia and TPSAB1 allele β tryptase duplication, a case report

Introduction: Described since 2014, hyper alpha Tryptasemia, is the first genetic trait responsible for a change in mast cell phenotype with increased tryptase secretion. This is caused by a duplication/triplication of the TPSAB1 gene encoding ⍺ tryptase (1). We report here the case of a patient also presenting with hypertryptasemia associated with a duplication ofTPSAB1 gene encoding not ⍺ tryptase but β tryptase.

Case description: We describe the case of a 36-year-old female patient presenting with chronic urticaria with angioedema. These urticarial episodes are diffuse, almost daily, and resistant to antihistamines. Elevated basal tryptase levels were found on several samples, ranging from 7.04μg/l to 13.2 μg/l. In view of this atypical picture, TPSAB1 mutation testing was requested,finding a β β β: β β genotype

Discussion: TPSAB1 is a dimorphic gene, encoding both α-tryptase and β-tryptase. The tryptase locus contains large segments of homologous repetitive sequences that facilitate gene conversion and replication (2). In the literature, genotypes with an increased copy of the β allele are relatively little described. Most of these articles report no significant increase in basal tryptase or clinical features (1)(3).

Conclusion: To our knowledge, this case is the first in the literature describing chronic urticaria with elevated basal tryptase associated with a β β β :β β β genotype.

References:

1. Glover SC, Carter MC, Korošec P, Bonadonna P, Schwartz LB, Milner JD, etal. Clinical relevance of inherited genetic differences in human tryptases. Ann AllergyAsthma Immunol. déc 2021;127(6):638‑47.

2. Fukuoka Y, Schwartz LB. Active monomers of human beta-tryptase haveexpanded substrate specificities. Int Immunopharmacol. 20 déc 2007;7(14):1900‑8.

3. Lyons JJ, Sun G, Stone KD, Nelson C, Wisch L, O’Brien M, et al. Mendelianinheritance of elevated serum tryptase associated with atopy and connective tissueabnormalities. J Allergy Clin Immunol. mai 2014;133(5):1471‑4