Impaired digestive function of sucrase-isomaltase in a complex with the Greenlandic sucrase-isomaltase variant

Abstract

Sucrase isomaltase (SI) is the most prominent disaccharidase in the small intestine. Congenital sucrase-isomaltase deficiency (CSID) is an autosomal recessive disorder caused by variants in the SI gene.A homozygous frameshift mutation, c.273_274delAG (p.Gly92Leufs*8), has been identified in CSID in the Greenlandic population. This variant eliminates the luminal domain of SI and results in loss of its digestive function.Surprisingly, the truncated mutant is transport-competent and localized at the cell surface; it interacts avidly with wild type SI and negatively impacts its enzymatic function.The data propose that heterozygote carriers of p.Gly92Leufs*8 may also present with CSID symptoms.