D3.416 - Hereditary Alpha-Tryptasemia: A Case Series

Hereditary alpha-tryptasemia (HaT) is a hereditary condition characterized by an elevated copy number of the alpha/beta 1 tryptase gene and is thought to affect approximately 5% of the population. The basal serum mast cell tryptase (MCT) level is usually greater than or equal to 8.0 ng/ml. HaT has been linked to various manifestations, including severe allergic reactions, although subsequent studies have shown no clinical association.  As there is only limited clinical data on HAT, we analysed the clinical characteristics of patients with HAT followed in our clinics. 

Patients seen in the allergy service who were identified with an increased TPSAB1 gene copy number and diagnosed with HaT were reviewed retrospectively. Data regarding patient demographics and clinical features were collected from electronic records. 

The mean age of the patients was 52.8 ± 6.3 years (2 female, 3 male). The mean basal tryptase level of the patients was 20.3 ug/L (range 11.7 - 34.1 ug/L, normal < 11 ug/L). All of the patients were positive for an abnormal alpha tryptase genotype (TPSAB1 tandem duplication) and negative for c-kit. Patients had a variety of diagnoses, typically associated with an allergy service including urticaria and angioedema (80%), followed by rhinitis (60%), asthma (40%), food allergy (40%) and venom anaphylaxis (20%). 60% of patients reported improvement in symptoms after initiation of high-dose second-generation antihistamines. One patient was treated with omalizumab. One patient is receiving venom immunotherapy.

There were a wide variety of clinical diagnoses and presentations in our patients with HaT, without any specific or unique features. Although a raised basline tryptase is associated with HaT, it is common at a population level, and there were no obvious features to distinguish these patients from the wider cohort of allergy clinic patients.  Genetic testing is useful for confirming that HaT is the reason for a raised tryptase level, but it remains to be determined how much HaT does or does not contribute towards allergic disease.