Children with persistently elevated baseline serum tryptase and symptoms of mast cell activation are often subjected to extensive, invasive evaluations for mast cell disorders such as systemic mastocytosis or mast cell activation syndrome (MCAS). When acute tryptase levels do not show significant elevation during episodes, confirming a diagnosis becomes even more difficult and often inconclusive.

Early TPSAB1 copy number variation (CNV) testing should be considered in pediatric patients with elevated baseline tryptase levels to evaluate for hereditary alpha tryptasemia (HαT). HαT is an autosomal dominant genetic trait caused by extra copies of the TPSAB1 gene found in 4% to 6% of the population, leading to elevated basal tryptase and increased mast cell reactivity.1,2 Symptoms can manifest as cutaneous, gastrointestinal, atopic, musculoskeletal, autonomic, and neuropsychiatric.1 These

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