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Hereditary Alpha Tryptasemia: Survey of Concomitant Genetic Testing
Joseph H Butterfield, Arveen K Bhasin1, Leah L Ishmael2
1Divisions of Allergy, Asthma and Immunology, Mayo Clinic, Rochester, Minnesota, USA.
Insights
Hereditary alpha tryptasemia (HαT) affects 4-6% of the population. Genetic testing in HαT patients rarely reveals additional genetic abnormalities, suggesting HαT is usually not associated with other genetic disorders.
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.
Introduction:
Hereditary alpha tryptasemia (HαT) affects 4-6% of the general population. Inherited as a Mendelian dominant, HαT has a variable phenotypic expression. Many patients have no obvious symptoms. There is a dearth of reports of possible co-inheritance of other genetic abnormalities.
Methods:
We examined records of 69 Mayo Clinic patients with HαT for the results of any additional genetic studies obtained during routine or focused evaluations. Clinical records of patients evaluated for baseline tryptase values >8 ng/mL testing positive for the TPSAB1 mutation were reviewed. Screening genetic tests obtained during standard care and/or for evaluation of clinical symptoms were recorded as well as inciting symptoms that led to tryptase determination, the serum tryptase level, alpha- and beta-tryptase gene copy numbers, and the urinary mast cell mediator metabolites.
Results:
Bone marrow biopsies for systemic mastocytosis and the presence of either a KIT Asp816Val, or Janus kinase 2 Val617Phe mutation were negative. Genetic tests were diverse and included nearly 1,000 suspect genes in 1 case and one to several hundred in others. There was no genetic testing in 19 patients and normal genetic test findings in 37 patients. A group of 8 patients showed at least one genetic abnormality and in a group of 5 patients, both normal and abnormal genetic findings were present. There was no clustering of genetic tests or relation to the inciting symptoms.
Conclusion:
Genetic testing, often extensive, was obtained in 73% of these HαT patients. Most of these results were normal and did not suggest the presence of a concomitant genetic disorder.
