PERSISTENTLY ELEVATED BASELINE TRYPTASE - A CASE OF HEREDITARY ALPHA TRYPTASEMIA

Abstract

<h3>Introduction</h3> Hereditary Alpha Tryptasemia (HaT) is an autosomal dominant genetic condition resulting from inheriting an extra <i>TPSAB1</i> gene copy, which encodes alpha and beta tryptase. Most cases involve increased copy numbers of alpha tryptase gene, but documented cases of beta tryptase gene duplications exist. HaT typically presents with tryptase levels greater than 8 ng/mL. Phenotypes vary in severity and history may include idiopathic anaphylaxis, vibratory urticaria, musculoskeletal problems, and dysautonomia. HaT can coexist with clonal mast cell diseases, particularly systemic mastocytosis (SM). <h3>Case Description</h3> A 15-year-old female presented for elevated blood tryptase levels. She reported frequent emesis, diarrhea, anorexia and unintentional weight loss. She reported generalized fatigue, anxiety, and musculoskeletal pain with 2-years of frequent flushing and postural orthostatic hypotension. She denied dysphagia, urticaria, and anaphylaxis. Lab evaluation revealed negative <i>c-KIT</i> mutation. Tryptase range was 12.2-14.2 ng/mL. <i>TPSAB1</i> gene analysis was obtained demonstrating two copies of alpha-tryptase and three copies of beta-tryptase. She was diagnosed with HaT based on a duplication at <i>TPSAB1</i> allele. Initiation of cromolyn and high dose cetirizine resulted in suboptimal symptomatic improvement. Management is currently ongoing. <h3>Discussion</h3> When assessing elevated tryptase levels, considering HaT in the differential diagnosis is important, in addition to possible confounding conditions. A diagnosis of HaT also does not preclude concomitant conditions such as SM. This case demonstrates the need for more inclusive nomenclature to account for beta-tryptase duplications sometimes presenting with similar clinical manifestations. We propose HaT be renamed Hereditary Tryptasemia, accounting for cases of additional beta-tryptase copies as demonstrated in this patient.