Some patients have fatigue, pain and gastrointestinal problems that look mast cellMast cell A type of white blood cell produced in the bone marrow. They help defend against infections and play a key role in allergic reactions. In SM, mast cells become overactive and build up throughout the body.-related, but they do not meet criteria for systemic mastocytosis (SM). New research points to hereditary alpha-tryptasemia (HαT), a genetic trait, as a possible cause. Findings were presented at the European Hematology Association (EHA) 2026 Congress, held June 11-14, 2026, in Stockholm, Sweden.
What is a mast cell?
Mast cells are specialized cells of the immune system that mediate inflammatory responses and allergic reactions. They are found in the body’s connective tissue.
Some people with HαT have no symptoms, while others experience symptoms across multiple body systems. Unlike SM, HαT doesn’t involve abnormal mast cell buildup.
People with HαT carry extra copies of TPSAB1, a gene involved in producing a protein called alpha-tryptaseTryptase A protein enzyme that is primarily produced by mast cells and stored in small pockets within the cells, known as granules. High levels of tryptase are a key indicator of SM.. This genetic difference can raise baseline serum tryptase (BST), a measure of the usual level of tryptase in the blood. Tryptase is a protein released by mast cells and used as a blood marker in mast cell-related conditions.
That matters because elevated BST can also be seen in SM, making the lab result harder to interpret unless HαT is considered. In SM, elevated BST has a different role. It is used as a diagnostic clue and as a marker of mast cell burden.
Learn more about the connection between HαT and SM
Researchers used the German Registry on Disorders of Eosinophils and Mast Cells to compare people with HαT only, SM only, both conditions or neither. The study aimed to describe symptom patterns and laboratory findings across groups defined by HαT and SM status.
This distinction may matter clinically because symptoms are not always explained by an SM diagnosis or BST level alone. Recognizing HαT may help doctors interpret persistent symptoms alongside BST results, especially in patients with mast cell-related complaints who do not meet criteria for SM.
The results showed a mismatch between laboratory findings and symptom burden. In the registry analysis, people with SM had higher BST levels overall, but those with HαT without SM had the highest symptom burden. “Although SM was associated with higher BST concentrations, overall symptom burden did not parallel BST levels,” the researchers wrote.
Pain-related and neurological symptoms were more prominent in HαT-positive patients, suggesting a distinct symptom profile in this group.
The findings may help explain why some patients with mast cell-related symptoms continue to report broad symptom burden even when they do not meet criteria for SM. They also suggest that HαT status may add useful context when doctors interpret BST results and symptom reports together.
Still, the study was designed to describe symptom and laboratory patterns, not to prove that HαT caused the symptoms or to test a treatment approach. More research is needed to understand how HαT may contribute to symptoms and how that information should guide care.
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