Hereditary Alpha Tryptasemia: Survey of Concomitant Genetic Testing.

Area of Science:

• Genetics
• Human Physiology

Background:

• Hereditary alpha tryptasemia (HαT) is a common genetic condition affecting 4-6% of the general population.
• HαT is inherited in an autosomal dominant pattern and exhibits variable clinical expressivity, with many individuals remaining asymptomatic.
• Limited data exists regarding the co-occurrence of other genetic abnormalities in HαT patients.

Purpose of the Study:

• To investigate the frequency and nature of additional genetic abnormalities in patients diagnosed with hereditary alpha tryptasemia (HαT).
• To determine if HαT is commonly associated with other inherited genetic conditions.

Main Methods:

• Retrospective review of medical records for 69 Mayo Clinic patients with HαT.
• Analysis of genetic testing results obtained during routine or specialized evaluations.
• Recording of clinical symptoms, serum tryptase levels, alpha- and beta-tryptase gene copy numbers, and mast cell mediator metabolites.

Main Results:

• Bone marrow biopsies and screening for KIT Asp816Val or JAK2 Val617Phe mutations were negative for systemic mastocytosis.
• Extensive genetic testing was performed in 73% of HαT patients, with results varying widely in scope.
• The majority of genetic tests yielded normal findings; only 8 patients showed at least one genetic abnormality, with no clear pattern or association with symptoms.

Conclusions:

• Most HαT patients undergoing genetic testing do not exhibit other concomitant genetic disorders.
• The findings suggest that HαT is infrequently associated with other identifiable genetic abnormalities.