S536 Prevalence of Disaccharidase Deficiencies in Adults with Irritable Bowel Syndrome and Functional Diarrhea: Interim Analysis from a Multicenter, Prospective U.S. Trial

Introduction: Disaccharidases are brush border enzymes that digest disaccharides to monosaccharides for absorption across the intestinal epithelium. Patients with disaccharidase deficiencies (DD) may experience post-prandial abdominal pain, bloating, flatulence, & diarrhea that can mimic Irritable Bowel Syndrome and diarrhea (IBS-D) & functional diarrhea (FD). While well-characterized in children, the prevalence of DDs in symptomatic adults is poorly defined. Methods: In this ongoing study, adult ( >18 yrs) patients fulfilling Rome IV diagnostic criteria for IBS-D or FD were recruited at Michigan Medicine (UM) & the University of Texas Health Science Center at Houston (UTH). Exclusion criteria included pregnancy, lactation, severe GI or abdominal co-morbidities, & history of previous GI surgeries excluding cholecystectomy or appendectomy. Eligible patients completed upper endoscopy (EGD) with 2-4 small intestinal biopsies collected from the duodenum distal to the ampulla of Vater. Biopsy samples underwent disaccharidase assay to measure disaccharidase activity (normal sucrase: >28.0 µM/min/g, maltase: >120.8 µM/min/g, lactase: >15.4 µM/min/g, palatinase: >9.8 µM/min/g, glucoamylase: >13.1 µM/min/g) using validated protocols at experienced reference labs (Arnold Palmer Hospital Labs & Joli Diagnostics, Inc.). Results: 154 patients (mean age = 45.6 yrs, 47% IBS-D, 53% FD, 74% female, 87% white) were enrolled & underwent EGD with biopsies collected to test for DD. More than a third of patients (56/154, 36.4%) had >1 DD. The most common DD was for lactase, found in 54 (35.1%) patients. Eleven patients (7.1%) tested positive for Sucrase-Isomaltase deficiency. Glucoamylase & palatinase deficiencies were each identified at 5%. Only lactase deficiency occurred in isolation. All patients with non-lactase deficiencies had other DDs, with at least 27% of these patients having pan-DDs (Table). The prevalence of the DDs were almost identical at both sites (Figure). Conclusion: More than 36% of US adult patients with IBS-D or FD had >1 DD. Lactase deficiency was the most common DD & the most likely to occur in isolation. Sucrase & maltase deficiencies were identified in approximately 1 in 14 symptomatic patients, & typically associated with at least 1 other DD. Lactase & non-lactase DD may be important & overlooked causes for symptoms in US patients with IBS-D or FD.Figure 1.: Disaccharidase deficiency prevalence rates by study site. **Glucoamylase was not measured for patients recruited by and screened at UTH. Table 1. - Characterization of Disaccharidase Deficiencies (A, Top) Prevalence of single or multi-enzymatic deficiencies by disaccharidase (B, Bottom) Prevalence of enzymatic deficiency overlap by disaccharidase A Total < 1 Def 1 Def 2 Def 3 Def 4 Def 5 Def Total 154 63.64% 27.27% 2.60% 1.95% 2.60% 1.95% Sucrase 11 0% 0% 9.09% 27.27% 36.36% 27.27% Maltase 11 0% 0% 18.18% 27.27% 27.27% 27.27% Lactase 54 0% 77.78% 5.56% 3.70% 7.41% 5.56% Palatinase 8 0% 0% 12.50% 12.50% 37.50% 37.50% Glucoamlyase 6 0% 0% 16.67% 0% 33.33% 50.00% B Sucrase Maltase Lactase Palatinase Glucoamylase Total 11 11 54 8 6 Sucrase X 90.91% 16.67% 87.50% 83.33% Maltase 90.91% X 16.67% 75.00% 66.67% Lactase 81.82% 81.82% X 87.50% 100.00% Palatinase 63.64% 54.55% 12.96% X 66.67% Glucoamylase 62.50% 57.14% 15.00% 66.67% X