A new review has analyzed the latest evidence on the genetics, presentation, and classification of systemic mastocytosis (SM) and notes the increased prevalence of a new genetic trait, hereditary alpha tryptasemia (HαT), in patients with SM.

The review, published in Acta Clinica Belgica, notes that patients with concurrent HαT and SM are at significant risk of anaphylaxis.

“Several studies show that an increased prevalence of HαT-carriers was found among patients with SM, especially in patients with ISM [indolent systemic mastocytosis],” the authors wrote. “Increased number of alpha copies of the TPSAB1 gene is now considered as an additional biomarker in the risk-assessment of severe anaphylaxis in patients with SM.”

The authors note that the link between the two conditions, as well as the underlying mechanisms involved, have yet to be elucidated. Rather than cause specific phenotypes, the HαT trait might alter the expression of multifactorial allergic diseases. Whether HαT itself manifests as a phenotypic syndrome with symptoms similar to SM is controversial.

Read more about SM comorbidities

Given that HαT has an autosomal dominant pattern of inheritance, the authors suggest genetic testing for family members of any individual who presents with symptoms and has a baseline serum tryptase greater than 8 ng/mL, which is commonly caused by HαT. Other authors have found that the subset of patients with SM who were HαT carriers had higher baseline serum tryptase levels, a much lower KIT D816V allele burden, and more severe symptoms than noncarriers.

The research team highlights the significantly increased risk of anaphylaxis in patients with concurrent HαT and mastocytosis and recommends preventive measures, including 2 adrenaline autoinjectors and lifelong venom immunotherapy in patients with IgE-mediated Hymenoptera venom allergy. In addition, patient education regarding how to recognize signs of anaphylaxis and how to use their injectors is essential.

Reference

Beyens M, Elst J, van der Poorten ML, et al. Mastocytosis and related entities: a practical roadmap. Acta Clin Belg. Published online October 19, 2022. 2022. doi:10.1080/17843286.2022.2137631