Hereditary alpha tryptasemia and clinical implications

Table 1 Conditions associated with high serum basal tryptase levels

Etiology	Diagnostic methods	Serum basal tryptase range	Incidence
Hereditary alpha tryptasemia	ddPCR	8-50 ng/mL	≤ 67%
No disease is detected	Exclusion diagnosis	Variable	≤ 23%
Renal failure	Glomerular filtration rate < 60 mL/minute, elevated creatinine	10-50 ng/mL	≤ 16%
Systemic mastocytosis	Bone marrow aspiration, c-KIT D816V mutation by ddPCR, skin biopsy	20-200 ng/mL	≤ 5%
Other myeloid neoplasms, acute myeloid leukemia, myeloproliferative neoplasms, myeloid neoplasms with eosinophilia, myelodysplastic neoplasms	Complete blood count, bone marrow aspiration, molecular genetics, cytogenetics	15-50 ng/mL	Rare
Hypereosinophilic syndrome	Bone marrow aspiration, molecular genetics, cytogenetics	10-50 ng/mL	Rare
Chronic inflammatory diseases, rheumatoid arthritis, eosinophilic esophagitis	Rheumatological examinations, endoscopy, biopsy	5-25 ng/mL	Rare

ddPCR: Digital droplet PCR; KIT: Tyrosine kinase protein.

Table 2 Clinical findings in hereditary alpha tryptasemia

Clinical findings
Gastrointestinal symptoms	Nausea
	Abdominal pain
	Diarrhea
	Vomiting
	Dyspepsia
Neuropsychiatric findings	Cognitive disorders (such as memory disorders)
	Fatigue
	Sleep disorders
	Depressive disorders
	Nervousness
Cutaneous and allergic symptoms	Sudden hot flushes
	Pruritus
	Rash, urticaria
Pain	Muscle pain
	Headache
	Joint pain
Other findings	Systemic sudden hypersensitivity reaction
	Joint hypermobility

Table 3 Common indications for genetic testing for hereditary alpha tryptasemia

sBT level ≥ 8 ng/mL
Recurrent signs of MC activation with unclear etiology (such as idiopathic anaphylaxis)
Suspected SM with negative c-KIT D816V, but very high TPS level
SM or MCAS with severe mediator-related symptoms
Serum TPS value > 15.0 ng/mL without underlying mastocytosis or myeloid neoplasm
Familial clustering of systemic MC activation symptoms
Higher levels of sBT according to the degree of bone marrow mast cell infiltration
Diagnosed or suspected idiopathic or secondary MCAS

MC: Mast cell; MCAS: Mast cell activation syndrome; sBT: Serum basal tryptase; SM: Systemic mastocytosis; TPS: Tryptase; KIT: Tyrosine kinase protein.