Understanding the Genetics of CSID

According to current knowledge, CSID is an autosomal recessive disorder of the sucrase-isomaltase gene (SI). To review basic genetics, each person has twenty-two non-sex (autosome) chromosomes and one sex chromosome from each parent for a total of forty-six chromosomes. All of our genes are located on these chromosomes which are located in our cells. These genes are our blueprints for how our bodies will grow, develop, and function. When the information in a gene is changed (mutated or faulty), the information sent to our cells is wrong. A mutation in a gene on one of the first twenty-two non-sex chromosomes can lead to an autosomal (non-sex) disorder such as CSID. Recessive inheritance means both genes in a pair must be defective in the same way to cause disease. People with only one defective gene in the pair are considered carriers. However, they can pass the abnormal gene to their children. Recent research (Uhrich S, Wu Z, Huang J, et al., 2012) suggests that some carriers of CSID may display symptoms.


If you are born to parents who both carry a recessive mutation for CSID, you have a 1 in 4 chance of getting the malfunctioning genes from both parents and developing CSID. You have a 50% (1 in 2) chance of inheriting one abnormal gene which would make you a carrier of CSID.


In other words, if four children are born to two people who both carry the gene (but do not have signs of disease), the statistical expectation is as follows:

    • One child is born with two normal genes (normal, no CSID)
    • Two children are born with one normal and one abnormal gene (carriers, without CSID)
    • One child is born with two abnormal genes (at risk for CSID)


Of the 46 chromosomes, the sucrase-isomaltase (SI) gene is located on chromosome 3. Although the SI gene is one gene, one part of the gene is responsible for making the enzyme sucrase and another part of the gene is responsible for making the enzyme isomaltase. In a recent study (Uhrich S, Wu Z, Huang J, et al, 2012), thirty-four CSID patients had their SI gene sequenced to look for mutations of the SI gene. Genetic mutations that cause CSID alter the structure, disrupt the production, or impair the function of sucrase-isomaltase. Twenty-six different mutations were identified with four of these twenty-six mutations detected more frequently than the other 22. The four most common SI gene mutations were G1073D, F1745C, V577G, and R1124X. A majority of the mutations were present in the sucrase area of the SI gene (57%) compared to the number of mutations in the isomaltase area (43%), even though the isomaltase area is larger than the sucrase domain. This emphasized why most CSID patients have little to no sucrase activity and varying degrees of isomaltase activity in their disaccharidase enzyme results from small bowel biopsy. At least one of these four mutations was present in 80% of thirty-four CSID patients. These four mutations are also present in 0.5% of normal controls. This means that there could be up to approximately one million carriers of CSID in the United States, which represents approximately 4% of the general population. Further studies are underway to determine the prevalence of CSID.


Due to the relatively large number of genetic mutations that were discovered in a relatively small sample size, there are significant differences of symptoms experienced in patients with CSID. These differences in symptoms are known as phenotypic variation. All patients lack sucrase activity, but some have normal isomaltase activity, some have only traces of isomaltase activity, and others have reduced, but sufficient isomaltase activity.


The genetic makeup of a patient with CSID shows mutations or variants. These genetic mutations or variants cause functional gastrointestinal problems such as diarrhea, recurrent abdominal pain, and bloating. Because these symptoms are similar to many other gastrointestinal disorders such as Irritable Bowel Syndrome (IBS), some scientists believe that a small percentage of patients who are diagnosed with IBS may actually have CSID. Further studies are underway and could help more accurately determine the prevalence of CSID in those patients that have been diagnosed with IBS. It is possible that a significant proportion of affected pediatric and adult patients are not being tested, and therefore not being diagnosed with CSID. For more information regarding a genetic prevalence screening study to test whether genetic mutations in the sucrase-isomaltase gene are common in the IBS-type patient population, and whether these mutations cause gastrointestinal problems, call 1.866.469.3773 to inquire about QOL Medical clinical trials.