267 Familial Cases of Mast Cell Disease

Abstract

Elevated mast cell numbers have been implicated in a wide range of clinical conditions, from allergic rhinitis and asthma to systemic mastocytosis. Familial etiologies for mast cell disease have been suggested including defects in c-kit regulation.PurposeTo evaluate a family with multiple presentations of probable mast cell disease.MethodsA case review of a family cohort is presented.SummaryThe index case, a 26-year-old Caucasian male, was initially followed at our institution for reversible airway obstruction as a young child. He was lost to follow-up, returning to the allergy/immunology clinic at the age of 18 years with fixed airway obstruction and severe, steroid-dependent asthma, as well as allergic rhinitis, GER, dilated cardiomyopathy of unknown etiology, and sleep apnea. Due to the refractory nature of his disease,and his continued decline on aggressive medical therapy, he underwent extensive evaluation, ultimately including endobronchial and open lung biopsies. Prior to biopsy, findings included a normal high-resolution chest CT, normal plethysmography, normal sweat chloride, normal α1-antitrypsin, normal CBC (with no eosinophilia), and an elevated IgE (1295 IU/mL). Biopsy showed chronic airway inflammation (eosinophils and neutrophils) plus an abundance of mast cells. Based on his biopsy results, cyclosporin and a leukotriene receptor antagonist were added to his treatment regimen with little clinical improvement. Our index patient is now the father of two children: a 4-year-old daughter (patient 2) with mild asthma and a 3-year-old son (patient 3) who has been diagnosed with systemic mastocytosis (with urticaria pigmentosa and GI involvement), moderate asthma, and allergic rhinitis. Patient 3 is currently followed at our institution for his mast cell disease. He has had urticaria pigmentosa lesions and severe reflux since birth, and he developed a GI bleed at 21 months of age. EGD revealed gastritis with increased mast cells on biopsy. A bone marrow aspirate and biopsy, abdominal ultrasonography, and bone scan were performed and showed no evidence of mastocytosis. Skin biopsy showed mast cell infiltration. Urine histamine was elevated (614 nmol/g), though both N-methylhistamine and serum tryptase were within normal range. His mastocytosis and atopic disease are under good control currently.ConclusionsThis case report suggests a familial defect leading to mast cell disease of varying clinical presentation. Further genetic evaluation is warranted and may prove valuable for future targeted therapy.

Familial Occurrence of Systemic Mast Cell Activation Disease

“…Similarly, in three of the five previous case reports on familial MCAD variability in the disease subtype, the severity of mediator-related symptoms, and the age at clinical onset within the MCAD sufferers has been described [9], [12], [23]. In four of those five case reports [10]–[13] functionally activating somatic point mutations were identified in mast cells which, however, were homotypic, i.e.…”

“…To date, only five familial cases (three SM and two MCAS) have been reported [9]–[13]. A systematic investigation of familial clustering would be an important step towards defining the contribution of inherited genetic factors to the risk of systemic MCAD.…”

Systemic mast cell activation disease: the role of molecular genetic alterations in pathogenesis, heritability and diagnostics

“… and Bursztein et al . 2009 . The prevalence of systemic MCAD among the first‐degree relatives in our sample was 33% (Figure ), which differed significantly ( P < 0·0001; Fisher′s exact test) from the prevalence in the control group (around 14%; Figure ).…”

“…In a second SM family, a functionally activating mutation in Kit exon 8, which resulted in the deletion of codon 419, was detected in the three affected patients (mother, daughter, granddaughter) but not in the healthy sister . One MCAS family has also been reported in which the father and his two children (daughter and son) presented with varying clinical features . However, the underlying genetic alterations were not investigated.…”

“…69 One MCAS family has also been reported in which the father and his two children (daughter and son) presented with varying clinical features. 70 However, the underlying genetic alterations were not investigated.…”