Hypomorphic SI genetic variants are associated with childhood chronic loose stools

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Carbohydrate Metabolism, Inborn Errors / epidemiology
  • Carbohydrate Metabolism, Inborn Errors / genetics
  • Carbohydrate Metabolism, Inborn Errors / pathology*
  • Child
  • Databases, Factual
  • Female
  • Genotype
  • Heterozygote
  • Humans
  • Male
  • Polymorphism, Single Nucleotide
  • Prevalence
  • Prospective Studies
  • Sucrase-Isomaltase Complex / deficiency*
  • Sucrase-Isomaltase Complex / genetics*


  • Sucrase-Isomaltase Complex

Supplementary concepts

  • Sucrase-isomaltase deficiency, congenital