RESUMO
BACKGROUND: Hereditary alpha-tryptasemia (HAT) is a genetic trait caused by an increased alpha-tryptase tryptase alpha/beta 1 gene copy number. Basal serum mast cell tryptase (MCT) level is typically greater than or equal to 8.0 ng/mL. OBJECTIVES: To study the clinical disease spectrum of HAT and determine its UK prevalence. METHODS: Droplet digital PCR was used to determine tryptase alpha/beta 1 copy number in 432 DNA samples from an unselected UK birth cohort and in 70 patients referred with a basal MCT level greater than 8 ng/mL. Baseline MCT concentrations and clinical presentation were also assessed in 4283 samples sent to a regional immunology laboratory. RESULTS: Duplication in alpha copy number was present in 5% of the unselected British birth cohort, with all affected individuals having a basal MCT level of greater than or equal to 8.0 ng/mL. Basal MCT levels of greater than or equal to 8.0 ng/mL were also found in 5% of the 4283 individuals referred for MCT testing because of clinical symptoms. In 70 patients confirmed to have HAT (79% with a duplication; 21% with a higher alpha gene copy number), urticaria/angioedema (51%), skin flushing (41%), food intolerances (39%), and altered bowel habits (36%) were common presenting complaints. However, clinical manifestations were not more common in patients with gene triplications or quintuplications than in those with duplications. Some immediate family members with the same genetic trait and high basal MCT levels were asymptomatic. CONCLUSIONS: Five percent of people in the United Kingdom may have HAT. The diagnosis should be considered when basal MCT level is greater than or equal to 8 ng/mL. HAT has variable clinical penetrance. It may modify the expression of multifactorial allergic diseases rather than directly cause specific phenotypes.