Genetic sucrase-isomaltase deficiency: epidemiology, clinical spectrum, and diagnostic challenge

The sucrase-isomaltase (SI) gene encodes sucrase-isomaltase enzyme found on the intestinal brush-border that has a major function in the hydrolysis of sucrose, oligosaccharides, and starch. Mutations disrupting its function cause genetic sucrase-isomaltase deficiency (GSID). Variants leading to mild to moderate reductions in enzyme activity may mimic disorders of gut-brain interaction (DGBI), and differentiating the etiology is crucial for initiating appropriate treatment. In this study, we aim to determine the rate of GSID in individuals who underwent whole exome or clinical exome sequencing (WES/CES) for indications other than chronic gastrointestinal symptoms in a single-center cohort. We also focused on a second group, the pediatric DGBI patients, who underwent SI gene analysis, to evaluate the rate of GSID in pediatric DGBI patients and assess the clinical utility of SI gene testing in GSID diagnosis.

We retrospectively reviewed 980 patients who underwent WES/CES between 2017-2022, and 148 pediatric patients with DGBI evaluated between May 2021 and August 2022 who received SI gene analysis.

The frequency of symptomatic GSID was found to be 0.3% among patients who underwent WES/CES, whereas it was 10% among pediatric DGBI patients. In DGBI patients carrying SI gene mutations, clinical improvement with a sucrose- and starch-free diet in combination with a sacrosidase response proved effective for establishing a diagnosis in all cases.

GSID has been frequently detected among pediatric DGBI patients. SI gene analysis combined with a sucrose-restricted diet and a sacrosidase challenge provides a reliable, non-invasive approach for definitive diagnosis.