According to current knowledge, Genetic Sucrase-Isomaltase Deficiency/Congenital Sucrase-Isomaltase Deficiency 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 or variant in a gene on one of the first twenty-two non-sex chromosomes can lead to an autosomal (non-sex) disorder such as Genetic Sucrase-Isomaltase Deficiency. 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 the Genetic Sucrase-Isomaltase Deficiency gene may display symptoms.
If you are born to parents who both carry a recessive mutation or variant for Genetic Sucrase-Isomaltase Deficiency, you have a 1 in 4 chance of getting the malfunctioning genes from both parents and developing Genetic Sucrase-Isomaltase Deficiency. You have a 50% (1 in 2) chance of inheriting one abnormal gene which would make you a carrier of Genetic Sucrase-Isomaltase Deficiency.
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:
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 Genetic Sucrase-Isomaltase Deficiency patients had their SI gene sequenced to look for mutations or variants of the SI gene. Genetic mutations or variants that cause Genetic Sucrase-Isomaltase Deficiency 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 or variants were G1073D, F1745C, V577G, and R1124X. A majority of the variants 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 Genetic Sucrase-Isomaltase Deficiency 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 variants was present in 80% of thirty-four Genetic Sucrase-Isomaltase Deficiency patients. These four variants are also present in 0.5% of normal controls. This means that there could be up to approximately one million carriers of Genetic Sucrase-Isomaltase Deficiency/Congenital Sucrase-Isomaltase Deficiency in the United States, which represents approximately 4% of the general population. Further studies are underway to determine the prevalence of Genetic Sucrase-Isomaltase Deficiency/Congenital Sucrase-Isomaltase Deficiency.
Due to the relatively large number of genetic mutations or variants that were discovered in a relatively small sample size, there are significant differences of symptoms experienced in patients with Genetic Sucrase-Isomaltase Deficiency/Congenital Sucrase-Isomaltase Deficiency. 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 Genetic Sucrase-Isomaltase Deficiency 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 patients who are diagnosed with IBS may actually have Genetic Sucrase-Isomaltase Deficiency/Congenital Sucrase-Isomaltase Deficiency. Further studies are underway and could help more accurately determine the prevalence of Genetic Sucrase-Isomaltase Deficiency 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 Genetic Sucrase-Isomaltase Deficiency. For more information regarding a genetic prevalence screening study to test whether genetic variants in the sucrase-isomaltase gene are common in the IBS-type patient population, and whether these variants cause gastrointestinal problems, click this link www.CSIDgps.com. The primary design objective in the Genetic Sucrase-Isomaltase Deficiency/Congenital Sucrase-Isomaltase Deficiency Genetic Prevalence Screening Study is to increase knowledge of a new genetic screening test for Genetic Sucrase-Isomaltase Deficiency/Congenital Sucrase-Isomaltase Deficiency based on the prevalence of SI gene variants in children experiencing chronic, idiopathic diarrhea and/or abdominal pain. A secondary objective is to correlate SI genotypes with in vivo phenotypes measuring sucrase activity via a new 13C Sucrose Oxidation Breath Test.
Genetic Sucrase-Isomaltase Deficiency/Congenital Sucrase-Isomaltase Deficiency is a rare, autosomal recessively inherited disease. There is wide phenotypic heterogeneity in CSID, with symptoms ranging from absent or minimal to life-threatening. The symptoms are nonspecific and similar to other common gastrointestinal disorders. As such, it is likely that the true prevalence of Genetic Sucrase-Isomaltase Deficiency is underestimated, and that numerous patients suffering from chronic diarrhea and/or abdominal pain as a result of Genetic Sucrase-Isomaltase Deficiency, remain undiagnosed.
Past clinical studies of smaller population groups showed high rates of Genetic Sucrase-Isomaltase Deficiency (5-10% in Greenland Eskimos, 3-7% in Canadian native peoples, 3% in Alaskans of native ancestry). Estimates of the prevalence of Genetic Sucrase-Isomaltase Deficiency in other North American and European populations are lower- at 1 in 500 to 1 in 2000 among non-Hispanic Caucasians, which would equal approximately 0.2%. The rates are even lower in African-Americans and Caucasians of Hispanic descent. The prevalence for those people with a level of sucrase activity below the lower limit for the normal population was estimated in one study to be 8.9% in the United States population.