D3.415 - Clinical manifestations of Hereditary alpha-tryptasemia (HaT) in Patients with Mast Cell Activation Syndromes

Description of the clinical features in patients with a history of mast cell activation syndromes and HaT.

A total of sixteen patients with a history of anaphylactic reactions, Systemic Mastocytosis (SM) or Cutaneous Mastocytosis (CM) and serum basal tryptase (BST) values at or above normal limits (≥8 μg/L) were included in the study. Copy number testing of the TPSAB1 allele by digital droplet PCR was performed. A comparative evaluation of clinical phenotypes in patients with and without HaT was then undertaken.

Among the 16 patients studied, 56% were male, with a median age of 40.5 years (age range: 24 to 71 years). Of these patients, 5 had a pathological HaT genotype. Among the five patients, one was diagnosed with indolent SM, one with CM, and three with MCAS. All five patients carried a duplication of the TPSAB1 gene. The median BST value was 16 μg/L (range: 14.3-25.2), whereas only the patient with SM+HaT had a BST value >20 μg/L. Among the 12 patients diagnosed with Mastocytosis (SM or CM), 2 had an abnormal HaT genotype (16%). Out of the 5 patients, 4 developed anaphylactic reactions (Brown classification grade III), of which 2 to Hymenoptera, 1 to a certain drug, and 1 had an episode of idiopathic anaphylaxis. From laboratory testing, 2 of the 5 showed vitamin B12 deficiency. In terms of the clinical phenotype, 4/5 patients (80%) experienced symptoms of gastroesophageal reflux and sleep disturbances, 3/5 (60%) episodes of flushing/itching, headaches, irritable bowel syndrome and autonomic nervous system disorders, while 2/5 (40%) experienced arthralgia. All patients with HaT were treated with H1- and H2-antihistamines, resulting in partial symptomatic improvement. The patient with SM +HaT, who experienced an anaphylactic reaction to hymenoptera, received additional omalizumab.

HaT is a significant risk factor for severe mediator-induced symptoms, including anaphylaxis, in patients with mast cell activation disorders. TPSAB1 testing is integrated into diagnostic algorithms as a contemporary prognostic biomarker for managing these patients. Further studies should be conducted to highlight the possible involvement of HaT in the pathogenesis of diseases with clonal or non-clonal mast cell disorders.