Congenital sucrase-isomaltase deficiency (ORPHA:35122)
A rare, genetic, congenital carbohydrate intolerance disorder characterized by lack of endogenous sucrase activity, marked reduction in isomaltase activity, and moderate decrease in maltase activity, and clinically manifesting with diarrhea, abdominal pain and bloating, failure to thrive.
Epidemiology
The prevalence for the classical type in the European population is estimated at 1/5,000 but it is higher among the indigenous populations of Alaska, Greenland and Canada. Many cases are probably undiagnosed, especially in patients with milder phenotypes.
Clinical description
Onset is usually after weaning from breast milk or lactose-only formula to foods containing sucrose and/or starch. Clinical manifestations include osmotic diarrhea, abdominal bloating and discomfort, flatulence and vomiting. This may result in failure to thrive, dehydration and malnutrition. Mildly affected individuals may present with irritable bowel syndrome and loose/frequent stools. Symptom severity depends on residual sucrase and isomaltase activity, as well as the amount of sugar and starch consumed, and thus onset may be later in life. CSID may coexist with other disaccharidase deficiencies (e.g. lactase, maltase-glucoamylase and/or peptidase deficiencies).
Etiology
CSID is caused by mutations in genes encoding the brush-border membrane complex, sucrase-isomaltase (SI), which is required for the breakdown of sucrose and starch into monosaccharides. These can then readily be absorbed in the gut facilitated by specific monosaccharide transporters. Amylase (salivary and pancreatic) facilitates the limited digestion of nutritional starch leading to oligomers but debranching has to be catalyzed by isomaltase. The SI deficiency results in an accumulation of disaccharides and glucose-oligomers in the lumen of the gut, causing the abdominal symptoms.
Diagnostic methods
Diagnosis may be suspected after presentation with osmotic diarrhea, bloating, abdominal pain and failure to thrive. Duodenal or jejunal mucosal biopsy and assay of disaccharidases is the 'gold standard' diagnostic technique. Samples must be immediately frozen and transported frozen to the analytical lab as preanalytical errors result in false positive findings. Presumed diagnosis can be made by a flat sucrose tolerance test and development of gastrointestinal symptoms, or via the 13C-sucrose breath hydrogen test, which is neither specific nor sensitive. Genetic testing is both an alternative and a supplement to enzymatic studies.
Differential diagnosis
Differential diagnosis includes the numerous causes of chronic diarrhea (allergic gastroenteropathy, celiac disease, Crohn's disease, irritable bowel syndrome, infection, severe gastro-enteritis, cystic fibrosis, diverticulitis, lactose intolerance, glucose-galactose intolerance, and fructose intolerance) as well as secondary causes of sucrase-isomaltase deficiency (medication, environmental).
Antenatal diagnosis
Prenatal diagnosis is possible when there is an index case. Due to relatively good treatment options and outcome, prenatal diagnosis is rarely indicated.
Genetic counseling
CSID is transmitted as an autosomal-recessive or autosomal-dominant trait. Offspring of affected individuals are obligate carriers. Heterozygous carriers may also experience symptoms like irritable bowel syndrome.
Management and treatment
Treatment used to be based on a strict sucrose- and starch-restricted diet. However, this is challenging and mostly still associated with CSID- symptoms. Regular consultation with a dietician is strongly recommended. Adjuvant enzyme replacement therapy (ERT) with sacrosidase is recommended to aid in sucrose digestion. The amount of enzyme given has to be titrated based on the residual sucrose activity and the amount of sucrose in the diet. However, sacrosidase ERT does not correct starch maldigestion, patients under sacrosidase treatment are often not symptom-free and still have to stick to starch restriction. Other tailor-made enzyme preparations distributed by specialized pharmacists contain a combination of sacrosidase, amylase and amyloglucosidases, and facilites the complete digestion of starch to monomers. Vitamin supplementation is typically required in infants and children.
Prognosis
Dietary restriction typically reduces symptoms, but is not sufficient in most patients. Treatment with sacrosidase is effective but not able to mediate starch digestion, and starch-restriction is still necessary. Improved enzyme replacement therapy limits the need for starch restriction in many patients and, frequently, a normal unrestricted diet is possible.

                            Last update: 
                            September 2020


                            - Expert reviewer(s): 
                            Pr Anibh Martin DAS