Joseph H. Butterfield

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.

Background: Urine mast cell mediator levels have found significant clinical utility in supporting the diagnosis of various allergic disorders in the adult population. There are few studies on the range of these mediator levels in the children and its clinical utility. Objectives: We determined the range of the urine mast cell mediator levels in children. Methods: Pediatric allergy and community-based pediatric clinics including children with and without an allergic disorder, respectively, served as the source of the study. Baseline urine mast cell mediator levels were obtained for all children. Demographics, atopic disorders, clinical symptoms and response to medication were documented. Results: Urine 2,3-Dinor-11Beta-Prostaglandin F2 Alpha (BPG) values were significantly higher in children with an underlying allergic disorder when compared to those without. Stratification based on age, sex and allergic disorder was performed in patients with an allergic disorder. Urine Leukotriene E ₄ (LTE ₄ ) and n-Methylhistamine (NMH) were significantly correlated with age (Spearman’s rho -0.4874 and -0.6902 respectively). With every year of age, the level of the urine NMH decreased by 18 units and urine LTE ₄ by 3 units approximately. Urine LTE ₄ and NMH levels were significantly higher in males when compared to females. Urine BPG levels were not significantly affected by age or sex. Conclusion: Distribution of urine mast cell mediator levels are slightly different from the values derived from studies in the adult population. Urine mast cell mediators may provide clinical utility in the diagnosis and management of allergic disorders. Further large-scale studies are warranted to validate clinical utility.