Genetic Prevalence

Understanding the Genetics of Genetic Sucrase-Isomaltase Deficiency/Congenital Sucrase-Isomaltase Deficiency

According to current knowledge, Genetic Sucrase-Isomaltase Deficiency or Congenital Sucrase-Isomaltase Deficiency is an autosomal recessive disorder of the sucrase-isomaltase genes (SI). Each person has 22 non-sex (autosome) chromosomes and one sex chromosome from each parent for a total of 46 chromosomes. All of our genes are located on these chromosomes, which are located in our cells. These genes are our blueprints for synthesizing proteins and enzymes that determine how our bodies will grow, develop and function. When the information in a gene is different due to natural variances, the information sent to our cells could cause a malfunction. A variant in a gene on one of the first 22 non-sex chromosomes can lead to an autosomal (non-sex-linked) disorder such as Genetic Sucrase-Isomaltase Deficiency. Recessive inheritance means both genes in a pair must be miscoded in a way that causes disease. People with only one gene variant in the pair are considered carriers. However, they can pass the abnormal gene to their children. Additionally, recent research suggests that some carriers of the Genetic Sucrase-Isomaltase Deficiency gene may display symptoms. 1

If you are born to parents who both carry recessive variants for Genetic Sucrase-Isomaltase Deficiency, you have a 1 in 4 (25%) chance of inheriting two malfunctioning genes, one from each parent, and developing Genetic Sucrase-Isomaltase Deficiency. You have a 1 in 2 (50%) chance of inheriting one abnormal gene, which would make you a carrier of Genetic Sucrase-Isomaltase Deficiency and possibly symptomatic.

Csid autosomal recessive inheritance

Of the 46 chromosomes that all people have, 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, 34 Genetic Sucrase-Isomaltase Deficiency patients had their SI gene sequenced to look for variants of the SI gene.1 Genetic variants that cause Genetic Sucrase-Isomaltase Deficiency alter the structure, disrupt the production or impair the function of sucrase-isomaltase. Twenty-six different variants were identified with four of these 26 mutations detected more frequently than the other 22. The four most common SI gene variants were G1073D, F1745C, V577G and R1124X. At least one of these four variants was present in 80% of 34 Genetic Sucrase-Isomaltase Deficiency patients studied. These four variants were also present in 0.5% of normal controls. This means that there could be up to approximately two million carriers of Genetic Sucrase-Isomaltase Deficiency in the United States. Further studies are underway to determine the prevalence of Genetic 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 in the symptoms experienced by patients with Genetic 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 possibly 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) or Toddler’s Diarrhea, some scientists believe that patients who are diagnosed with IBS actually may have Genetic Sucrase-Isomaltase Deficiency. Further studies are underway to more accurately determine the prevalence of Genetic Sucrase-Isomaltase Deficiency in those patients diagnosed with IBS or Toddler’s Diarrhea. 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 on genetic testing to aid in the diagnosis of Sucrase-Isomaltase Deficiency, click here. A free SI Genetic Test kit is available to healthcare professionals.

How Common is Genetic Sucrase-Isomaltase Deficiency/Congenital Sucrase-Isomaltase Deficiency?

Genetic Sucrase-Isomaltase Deficiency/Congenital Sucrase-Isomaltase Deficiency is a rare, autosomal recessively inherited disease.2 There is wide phenotypic heterogeneity in Genetic Sucrase-Isomaltase Deficiency, 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.

gsid prevalence map

Estimated prevalence of CSID in various populations. 2

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).2 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% to 0.05%. The rates are thought to be even lower in African-Americans and Caucasians of Hispanic descent. The majority of identified variants cause a complete or almost complete lack of availability of both sucrase and isomaltase at the cell surface where the enzymes can act on food. The location of the genetic variant in either the sucrase or isomaltase region of the gene often results in a lack of both sucrase and isomaltase activity, and not necessarily a loss of activity of only one part of the two-part enzyme.

References

  1. Uhrich S, Wu Z, Huang J, Scott CR. Four Mutations in the SI Gene Are Responsible for the Majority of Clinical Symptoms of CSID. J Pediatr Gastroenterol Nutr. 2012; 55(2):S34-S35.
  2. Treem WR. Congenital sucrase-isomaltase deficiency. J Pediatr Gastroenterol Nutr. 1995;21:1-14.
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