Inborn errors of Metabolism

Congenital Sucrase-Isomaltase Deficiency (CSID)

Congenital Sucrase-Isomaltase Deficiency (CSID)
Congenital Sucrase-Isomaltase Deficiency (CSID) is an inherited enzyme deficiency disorder that affects a person’s ability to digest sucrose (table sugar) and starch. The prevalence of CSID is estimated to be between 1/500 and 1/2 000 among individuals of European descent. The condition is more prevalent in the native populations of Greenland, Alaska, and Canada, where as many as 1 in 20 people may be affected.


CSID can cause symptoms similar to Irritable Bowel Syndrome (IBS)
The intestinal enzyme sucrase-isomaltase (SI) is expressed in the brush border membrane of the small intestine, and aids in the breakdown of sucrose and starch into glucose and fructose. Patients with CSID have a mutation in the SI gene that results in lack of and/or impaired function of the SI enzyme. This leads to malabsorption and the sugar being fermented by the intestinal flora, which can cause symptoms similar to IBS, like diarrhea and abdominal pain, but also poor weight gain and failure to thrive.

CSID is a hereditary enzyme deficiency disorder
CSID is an autosomal recessive disease, which means that a person needs to inherit a mutated SI gene from both parents to develop the disorder. The SI gene is located on chromosome 3 and may be mutated in different ways. At present, more than 25 mutations in the gene responsible for the synthesis of SI have been discovered and about 80% of patients have at least one of the four most common mutations. These mutations result in a variety of defects and is reflected in a range of enzymatic capability ranging from completely absent activity to low but present residual activity.


Chronic diarrhea and abdominal pain are common symptoms of CSID
The symptoms of Congenital sucrase-isomaltase deficiency can vary between individuals, but usually becomes apparent after an infant is weaned and starts to consume fruits, juices, and grains. After ingestion of sucrose or maltose, an affected child will typically experience diarrhea, stomach cramps, bloating and excess gas production. These digestive problems can lead to malnutrition, failure to gain weight and grow at the expected rate (failure to thrive). Studies show that even carriers of just one mutated copy of the SI gene can experience symptoms

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How CSID is diagnosed
The diagnosis of CSID is often delayed, misdiagnosed or even missed and may be confused with a number of other diseases if not tested for specifically. Examples of differential diagnosis are congenital intestinal malformations, celiac disease, cystic fibrosis, chronic non-specific diarrhea, infectious and postinfectious diseases, lactose intolerance, endocrine disorders, pseudomembranous colitis and food allergy. Some patients with CSID have previously been diagnosed with IBS and research shows an association between IBS and mutations in the SI gene.

Methods to aid in the diagnosis of CSID:
  • The current standard method for diagnosing CSID is small bowel biopsy with disaccharidase enzyme activity testing. In this procedure, biopsies are taken from the small intestine, immediately frozen and sent to laboratory, and assayed for sucrase, isomaltase, lactase and maltase enzyme activity. CSID is usually characterized by absent or markedly reduced sucrose activity, reduced maltase and isomaltase activity, normal lactase activity and normal small bowel histology.
  • Genetic testing for the known SI gene mutations is a non-invasive test. The genetic test can determine whether a person suspected of having CSID has any of the mutations known to cause the disorder.
  • The Sucrose hydrogen breath test is another non-invasive test that can be used to aid in the diagnosis of CSID. An increase in breath hydrogen output after intake of sucrose indicates that the SI enzyme is not working properly. The test may give rise to suspicion of CSID, but data suggest that the test is an unreliable diagnostic parameter for CSID.

How CSID is treated
Treatment consists primarily of reducing the amount of sucrose and starch in the diet. However, adherence to a strict sucrose- and starch-free diet is challenging as much of the processed food we can buy today contains “table sugar” (sucrose). Follow-up studies of children with CSID treated with sucrose- and starch-restricted diets have demonstrated that 60%-75% of patients still experience diarrhea, gas, and/or abdominal pain. In the United States, enzyme replacement therapy has been available as an approved pharmacologic alternative to sucrose-free diets since 1998.

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  • National Library of Medicine (NLM)
  • Treem WR. Clinical aspects and treatment of congenital sucrase-isomaltase deficiency. J Pediatr Gastroenterol Nutr. 2012;55 (Suppl 2):S7-13
  • Uhrich et al. Four mutations in the SI Gene are responsible for the majority of clinical symptoms of CSID. J Pediatr Gastroenterol Nutr. 2012;55 (Suppl 2):S34-35
  • Cohen S. The clinical consequences of sucrase-isomaltase deficiency. Molecular and Cellular Pediatrics 2016
  • Henström et al. Functional variants in the sucrase-isomaltase gene associate with increased risk of irritable bowel syndrome. Gut 2016