Tryptase genotyping plays a growing role in identifying, diagnosing and managing systemic mastocytosis (SM), providing a clearer understanding of tryptase levels and guiding important decisions such as when to perform a bone marrow biopsy, according to a study published recently in Frontiers in Allergy.
By adjusting basal serum tryptase (BST) reference ranges based on a person’s genetic copy number of the TPSAB1 gene, clinicians can now better interpret whether a patient’s tryptase level is truly abnormal or if it simply reflects inherited variation.
Mastocytosis is a disease marked by the buildup of mast cells in the body, and levels of BST are often used as a marker of disease burden. However, high BST levels are not always due to mast cell disease. Some people have elevated BST due to increased alpha-tryptase gene copies, a condition known as hereditary alpha tryptasemia.
A type of genetic testing called tryptase genotyping — usually done with digital droplet PCR — measures both alpha and beta tryptase gene copies and aligns BST interpretation with a person’s genetics.
“Tryptase and tryptase genotyping assessments are essential in the screening, diagnosis, and management of SM,” explained this study’s authors. “Patients with an elevated BST based upon their tryptase genotype should be offered a BM biopsy at a center with a hematopathologist expert to evaluate for SM.”
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This approach is especially helpful in patients with non-advanced SM forms such as bone marrow mastocytosis or indolent SM. In these cases, a BST level that appears high may actually be normal for someone with extra TPSAB1 copies. On the other hand, if the BST is higher than expected based on the genotype, this may signal true mast cell disease, prompting a bone marrow biopsy and expert evaluation.
Tryptase levels are part of the World Health Organization’s diagnostic criteria for SM, with BST over 20 ng/mL counting as a minor criterion and values above 200 ng/mL considered a B-finding indicating higher disease activity. Genotyping refines how clinicians apply these cutoffs by revealing whether the elevation is due to SM or inherited traits.
In patients treated with tyrosine kinase inhibitors, which have varying effects on mutant and normal KIT proteins, BST may remain elevated in those with hereditary alpha tryptasemia even when their disease is under control. This makes genotype-informed BST interpretation essential to avoid misreading treatment response and determining when to re-evaluate the bone marrow.
Ultimately, tryptase genotyping enhances accuracy in SM care, helping clinicians decide who needs further testing and who can avoid unnecessary procedures. Patients benefit from a more personalized approach that respects both their disease and their genetics.
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