Hereditary Alpha-Tryptasemia: UK Prevalence and Variability in Disease Expression

Area of Science:

• Genetics
• Immunology
• Allergy

Background:

• Hereditary alpha-tryptasemia (HAT) is a genetic condition linked to increased alpha-tryptase gene copy number.
• Individuals with HAT typically exhibit basal serum mast cell tryptase (MCT) levels of 8.0 ng/mL or higher.

Purpose of the Study:

• To investigate the clinical manifestations and prevalence of Hereditary alpha-tryptasemia (HAT) in the UK.
• To establish the diagnostic threshold for basal serum mast cell tryptase (MCT) in HAT.

Main Methods:

• Droplet digital PCR was employed to quantify alpha-tryptase gene copy number in a UK birth cohort and symptomatic individuals.
• Serum MCT levels and clinical data were analyzed from 4283 individuals referred for MCT testing.

Main Results:

• HAT was identified in 5% of the UK birth cohort, all with basal MCT levels ≥ 8.0 ng/mL.
• Common symptoms in confirmed HAT patients included urticaria/angioedema, skin flushing, food intolerances, and altered bowel habits.
• Clinical presentation varied, with some family members with HAT and elevated MCT levels remaining asymptomatic.

Conclusions:

• Approximately 5% of the UK population may have HAT, indicated by basal MCT levels ≥ 8.0 ng/mL.
• HAT exhibits variable clinical penetrance and may modulate rather than directly cause specific allergic phenotypes.