Extended multisystem manifestations of hereditary α-tryptasemia in an allergy center cohort

Hereditary α-tryptasemia (HαT) is a common autosomal-dominant trait caused by additional copies of the gene TPSAB1 encoding for α-tryptase. This inheritance is the most common etiology for elevated basal serum tryptase (BST), occurring almost exclusively at BST ≥ 8 μg/L. In systemic mastocytosis (SM) and nonclonal mast cell-mediated disorders, HαT is linked to a complex constellation of symptoms.

We sought to delineate the spectrum and burden of extended manifestations observed in patients with and without HαT presenting to an allergy department.

A total of 332 allergy patients with BST ≥ 8 μg/L were prospectively enrolled. Blood was tested for HαT and KIT ^D816V mutation (to identify patients with SM) by digital droplet PCR. Symptom assessment was conducted with a HαT-customized questionnaire (n = 256).

HαT-positive patients reported a significantly higher symptom burden than HαT-negative patients (9.3 vs 6.5; P < .001), particularly those referred for urticaria/angioedema (8.9 vs 5.5; P = .023) and atopic diseases (8.3 vs 4.2; P = .016). In allergy patients with HαT, symptom spectrum was extended to fatigue (+26%; P < .001), sleep disturbances (+13%; P = .049), and neuropsychiatric symptoms such as concentration issues (+26%; P < .001), memory impairment (+16%; P = .020), sadness/lack of motivation (+22%; P = .004), headaches (+19%; P = .006), abdominal pain (+21%; P = .002), and cardiovascular symptoms such as dizziness (+14%; P = .052), palpitations (+15%; P = .039), and orthostatic dysregulation (+22%; P = .002).

HαT may have a broader clinical impact beyond classic allergy-immunology connections and may be associated with extended clinical phenotypes. This suggests an integrative approach to medical practice in allergy patients.