PLoS One. 2020 May 20;15(5):e0231891. doi: 10.1371/journal.pone.0231891. eCollection 2020.

Bruno P Chumpitazi ¹, Jeffery Lewis ², Derick Cooper ³, Mauro D'Amato ⁴, Joel Lim ⁵, Sandeep Gupta ⁶, Adrian Miranda ⁷, Natalie Terry ⁸, Devendra Mehta ⁹, Ann Scheimann ¹⁰, Molly O'Gorman ¹¹, Neelesh Tipnis ¹², Yinka Davies ⁶, Joel Friedlander ¹³, Heather Smith ³, Jaya Punati ¹⁴, Julie Khlevner ¹⁵, Mala Setty ¹⁶, Carlo Di Lorenzo ¹⁷

Author information

• ¹Baylor College of Medicine, Houston, TX, United States of America.
• ²Children's Center for Digestive Health Care, Atlanta, GA, United States of America.
• ³QOL Medical, LLC, Vero Beach, FL, United States of America.
• ⁴School of Biological Sciences, Monash University, Clayton, VIC, Australia.
• ⁵Children's Mercy Hospital, Kansas City, MO, United States of America.
• ⁶Sacramento Pediatric Gastroenterology, Sacramento, CA, United States of America.
• ⁷Children's Hospital of Wisconsin, Milwaukee, WI, United States of America.
• ⁸Children's Hospital of Philadelphia, Philadelphia, PA, United States of America.
• ⁹Arnold Palmer Children's Hospital, Orlando, FL, United States of America.
• ¹⁰Johns Hopkins University, Baltimore, MD, United States of America.
• ¹¹Primary Children's Medical Center, Salt Lake City, UT, United States of America.
• ¹²University of Mississippi Medical Center, Jackson, MS, United States of America.
• ¹³Children's Hospital Colorado, Digestive Health Institute, University of Colorado School of Medicine, Aurora, CO, United States of America.
• ¹⁴Children's Hospital of Los Angeles, Los Angeles, CA, United States of America.
• ¹⁵Columbia University Medical Center, New York, NY, United States of America.
• ¹⁶UCSF Benioff Children's Hospital Oakland, Oakland, CA, United States of America.
• ¹⁷Department of Pediatrics, The Ohio State University, Columbus, OH, United States of America.

Abstract

Objective: The SI gene encodes the sucrase-isomaltase enzyme, a disaccharidase expressed in the intestinal brush border. Hypomorphic SI variants cause recessive congenital sucrase-isomaltase deficiency (CSID) and related gastrointestinal (GI) symptoms. Among children presenting with chronic, idiopathic loose stools, we assessed the prevalence of CSID-associated SI variants relative to the general population and the relative GI symptom burden associated with SI genotype within the study population.

Methods: A prospective study conducted at 18 centers enrolled 308 non-Hispanic white children ≤18 years old who were experiencing chronic, idiopathic, loose stools at least once per week for >4 weeks. Data on demographics, GI symptoms, and genotyping for 37 SI hypomorphic variants were collected. Race/ethnicity-matched SI data from the Exome Aggregation Consortium (ExAC) database was used as the general population reference.

Results: Compared with the general population, the cumulative prevalence of hypomorphic SI variants was significantly higher in the study population (4.5% vs. 1.3%, P < .01; OR = 3.5 [95% CI: 6.1, 2.0]). Within the study population, children with a hypomorphic SI variant had a more severe GI symptom burden than those without, including: more frequent episodes of loose stools (P < .01), higher overall stool frequency (P < .01), looser stool form (P = .01) and increased flatulence (P = .02).

Conclusion: Non-Hispanic white children with chronic idiopathic loose stools have a higher prevalence of CSID-associated hypomorphic SI variants than the general population. The GI symptom burden was greater among the study subjects with a hypomorphic SI variant than those without hypomorphic SI variants.