Differential Effects of Sucrase-Isomaltase Mutants on Its Trafficking and Function in Irritable Bowel Syndrome: Similarities to Congenital Sucrase-Isomaltase Deficiency

Nutrients. 2020 Dec 22;13(1):9. doi: 10.3390/nu13010009.

PMID: 33375084

Diab M Husein, Sandra Rizk, Hassan Y Naim

Highlights: In genetic screening of IBS patients, it is discovered that rare sucrase-isomaltase (SI) gene variants are associated with IBS. The findings of this article emphasize the importance of screening for SI mutations in IBS patients and considering enzyme replacement therapy as an appropriate treatment option, similar to CSID.

Abstract

Objective: Congenital sucrase-isomaltase deficiency (CSID) is a rare metabolic intestinal disorder in which sucrase-isomaltase (SI) activity is decreased or absent. Irritable bowel syndrome (IBS), a prevalent functional gastrointestinal condition with unknown etiology, shares many of the same symptoms as CSID. In genetic screening of IBS patients, it is discovered that rare SI gene variants are associated with IBS. The biochemical, cellular, and functional characteristics of some of these variants were investigated in this study. The results show that SI mutants can be divided into three groups: immature, mature but slowly transported, and mature and properly transported but with reduced enzymatic activity. It is also identified that SI mutant phenotypes that are deficient but generally not as severe as those seen in CSID patients.

Conclusion: The diverse effects of the SI mutations are analyzed in this study on trafficking and function. This analysis supports the idea that CSID and IBS are heterogeneous disorders, the severity of which is likely associated with the biochemical phenotypes of the SI mutants as well as the environment and diet of patients. The findings of this article highlight the importance of screening for SI mutations in IBS patients and considering enzyme replacement therapy as an appropriate treatment option, similar to CSID.

Keywords: congenital sucrase-isomaltase deficiency; irritable bowel syndrome; protein trafficking; sucrase-isomaltase.