Genetic and acquired sucrase-isomaltase deficiency: A clinical review

Genetic sucrase-isomaltase deficiency (GSID) is an inherited deficiency in the ability to digest sucrose and potentially starch due to mutations in the sucrase-isomaltase (SI) gene. Congenital sucrase-isomaltase deficiency is historically considered to be a rare condition affecting infants with chronic diarrhea as exposure to dietary sucrose begins. Growing evidence suggests that individuals with SI variants may present later in life, with symptoms overlapping with those of irritable bowel syndrome. The presence of SI genetic variants may, either alone or in combination, affect enzyme activity and lead to symptoms of different severity. As such, a more appropriate term for this inherited condition is GSID, with a recognition of a spectrum of severity and onset of presentation. Currently, disaccharidase assay on duodenal mucosal tissue homogenates is the gold standard in diagnosing SI deficiency. A deficiency in the SI enzyme can be present at birth (genetic) or acquired later, often in association with damage to the enteric brush-border membrane. Other noninvasive diagnostic alternatives such as sucrose breath tests may be useful but require further validation. Management of GSID is based on sucrose and potentially starch restriction tailored to the individual patients' tolerance and symptoms. As this approach may be challenging, additional treatment with commercially available sacrosidase is available. However, some patients may require continued starch restriction. Further research is needed to clarify the true prevalence of SI deficiency, the pathobiology of single SI heterozygous mutations, and to define optimal diagnostic and treatment algorithms in the pediatric population. What is Known Congenital sucrase-isomaltase deficiency is historically considered to be a rare autosomal recessive condition identified in infants with symptoms of diarrhea, malabsorption, and failure to thrive Single sucrase-isomaltase (SI) pathologic variants have been increasingly reported in children and adults with disorders of gut-brain interactionWhat is New SI genetic variants, express varying degrees of enzyme activity and lead to symptoms of varying severity that may present after infancy SI enzyme deficiency may be an important and overlooked cause of unexplained gastrointestinal symptoms Given the increasing awareness of genetic SI variants and their association with a spectrum of gastrointestinal symptom severity, a better term is genetic sucrase-isomaltase deficiency