Supplementary Material for: Hereditary Alpha Tryptasemia: Survey of Concomitant Genetic Testing

Abstract Background 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 1000 suspect genes in one 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.