alphatryptasemia

Alpha-tryptasemia is a human genetic variation characterized by an increased copy number of the TPSAB1 gene, which encodes the tryptase enzyme alpha-tryptase. This structural variation leads to higher production of alpha-tryptase and is associated with elevated baseline levels of serum tryptase compared with individuals without the variation. The trait is inherited and can be present in one or more family members.

Genetics and expression: TPSAB1 copy number changes are inherited in an autosomal fashion with variable expressivity. The number of extra copies tends to correlate with the magnitude of baseline tryptase elevations, but symptom burden varies widely among individuals.

Clinical significance: Alpha-tryptasemia itself is not a disease. Elevated baseline tryptase is a biomarker of mast cell activity, and some studies have reported associations with hypersensitivity reactions, venom allergies, or features compatible with mast cell activation syndromes, but evidence for consistent or specific clinical syndromes remains inconclusive. Many people with the trait remain asymptomatic.

Diagnosis and management: Diagnosis relies on genetic testing to determine TPSAB1 copy number, usually in combination with measurement of baseline serum tryptase. There is no disease-specific treatment; management focuses on addressing clinical symptoms if they occur, including careful perioperative planning and avoidance of known triggers. Genetic counseling may be offered because the trait can be inherited.

See also: Tryptase; Mast cell activation syndrome; Copy number variation; Genetic traits.