Adult sucrase-isomaltase deficiency masquerading as IBS

Recently in Gut, several publications reported an increased prevalence of hypomorphic (defective) sucrase-isomaltase ( SI ) gene variants in patients with irritable bowel syndrome (IBS),1 2 and the association with impaired cell-surface expression and reduced digestive function of the corresponding enzyme.3 In addition, hypomorphic SI carriers have shown reduced response compared with non-carriers in a low-FODMAP (fermentable oligo- di- mono-saccharides and polyols) trial of IBS patients with diarrhoea.4 These and other studies,5 6 including recent large population-based surveys,7 raise the question whether genetic defects in the SI gene may be sought to explain abdominal symptoms in some patients with IBS. A 23-year-old patient was referred with a diagnosis of IBS due to his long-standing postprandial diarrhoea associated with bloating, abdominal pain and nausea. He also had marked fatigue, headaches and mouth ulcers. He had symptoms since infancy without signs of malnutrition or failure-to-thrive. Extensive investigations excluded alternate causes of diarrhoea, including coeliac and inflammatory bowel disease, pancreatic exocrine insufficiency and bile acid diarrhoea. A low FODMAP diet worsened symptoms and psychological interventions were not helpful. We hypothesised the involvement of SI defects. Resequencing of the gene identified three coding variants of interest (H1684Q, G1760V and V15F), which were assigned to …