S2462 Hereditary Alpha Tryptasemia Syndrome (HαTS): An Autobiographical Case Report and Literature Review of an Under-Recognized Clinical Entity Emulating Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD)

Introduction: HαTS is an autosomal dominant disease first characterized in 2014 by Lyons JJ. et al. and present in ∼5% of the White population. HαTS is responsible for ∼90% of patients in the western world with elevated basal serum tryptase (eBST). It modifies clonal and nonclonal mast cell (MC) disorders with increased prevalence and/or severity of anaphylaxis and MC mediator-related symptoms. We aim to present an autobiographical case report and peer literature review of HαTS. Case Description/Methods: We conducted a review of peer literature selected using search terms: HαTS, Tryptase, IBS, IBD. Case: A 26-year-old male with a cc of change in bowel habits for 3 years, going from 1-2 formed stools to up to 6 loose bowel movements (BMs) per day. These are associated with excessive flatulence and crampy abdominal pain relieved by passage of BMs. GERD, nausea, and generalized pruritus worse at night which frequently awakens him from sleep. He also has chest and facial flushing with alcohol intake. No symptom relief from low-FODMAP or low-histamine diets, with relief of symptoms on a very low carbohydrate diet. Negative work up included allergy testing, celiac serology and HLA testing, brush border disaccharidases, CBC and CMP, thyroid panel, fecal elastase. VIP slightly elevated at 65 pg/mL (nl < 58.8 pg/mL). Endoscopy revealed small esophageal ulcer that resolved. Duodenal biopsies showed increased MC density at 24 per hpf (nl < 15 per hpf) and increased intraepithelial lymphocytosis. Colonoscopy with biopsies nl. Initial serum tryptase was 5.6 ng/mL, repeated 2 years was elevated to 11.4 ng/ml (nl < 6.5 ng/mL). Diagnosis: genetic PCR testing of buccal swab revealed extra-allelic copy of alpha tryptase gene on TPSAB1 gene locus, consistent with HαTS. Literature Review: HαTS presents with variable multisystemic symptoms with 1/3rd of patients asymptomatic, 1/3rd have mild disease, and 1/3rd have severe disease. Flushing, pruritis, dysautonomia, and symptoms emulating IBS and IBD with diarrhea present in 30-50%. Other symptoms may include food intolerances, IgE-mediated food allergies, neuropsychiatric symptoms, and joint hypermobility (Table). Discussion: HαTS should be considered in the differential for symptoms of IBS and IBD—especially when flushing, pruritis, or dysautonomia are present. This will prevent delay of diagnosis and reduce total costs. Duodenal biopsies showing increased density of MCs and elevated serum tryptase ( >6.5 ng/mL) are suspicious for HαTS. Genetic testing is confirmatory. Table 1. - Clinical features of HαTS, IBS, and IBD patients Clinical Feature HαTS IBS IBD Age of Onset Unknown 20-30 y/o Major peak 15-25 y/o, minor peak 50-70 Male:Female Male = Female Female > Male Male = Female Western Prevalence ∼5% of Whites 10-20% 1.3% Common Symptoms and Signs Diarrhea predominant, crampy abdominal, pain, GERD, flushing, and pruritus Diarrhea and/or constipation, crampy abdominal pain, GERD Diarrhea, crampy abdominal pain, bloody stools, bowel fistulas, intestinal strictures/fibrosis, weight loss, anemia Serum Lab Values Elevated Basal Serum Tryptase (Suspicion Mild-Moderate 6.2-7.9 ng/mL; Suspicion High >8.0 ng/mL) No significant findings Elevated C-reactive protein, erythrocyte sedimentation rate, fecal calprotectin, and Iron deficiency Genetic Characterization Extra allelic copy of alpha tryptase encoding gene on TPSAB1 gene locus2 Normal +/- Positive Small Bowel Histology Increased density of Mast Cells forming 2-15 cell clusters No significant findings Granulomas, Inflammation, crypt abscesses Current Treatments H1 and H2 antihistamines, Oral Cromolyn, Carbohydrate Restriction*, Compounded Oral Ketotifen**, Sub Q Omalizumab**, Other Biologics** See 2019 ACG Clinical Guidelines for IBS Immunomodulation Therapies *Treatment used successfully by patient in case study, but not described in literature.**Treatments reported in literature with variable responses and not used by patient in case study).