How Common Is CSID?

Congenital Sucrase-Isomaltase Deficiency (CSID) is considered a rare disease. Because its symptoms overlap with more common gastrointestinal disorders, it is often difficult to diagnose. It is likely that the true prevalence of CSID is underestimated and that numerous individuals suffering from chronic diarrhea and abdominal pain may have CSID but remain undiagnosed. Many of those with CSID may wait many years for a diagnosis because the incidence is so rare and the currently accepted diagnostic tools are invasive procedures. Recent clinical and genetic studies suggest that CSID is a more common disease than previously thought.1-11

In the past, clinical studies of small populations have found a high prevalence of CSID: 5% of Eskimos who were living in Greenland, 7% of Eskimos who were living in Canada, and 3% of Eskimos who were living in Alaska.12-14 At the same time, estimates of the prevalence of CSID in non-Hispanic White North Americans was lower, with a prevalence of approximately 2 in 1000 or 0.2%.15 In other studies, the prevalence was even lower in African-Americans.16

However, another older study of enzyme activity in biopsied tissue from 217 Americans estimated an 8.9% prevalence of individuals with a level of sucrase activity below the lower limit for the normal population, suggestive of a dominant pattern of inheritance and CSID-associated symptoms among heterozygotes (see Understanding the Genetics of CSID), was estimated in one study to be 8.9% in the United States population.15 The most recent and largest study to estimate CSID prevalence was a review of clinical findings for 27,875 patients who were referred by a gastroenterologist for endoscopic biopsy and enzyme analysis to diagnose the cause of their chronic gastrointestinal symptoms. In this study, 9.3% were found to have deficient sucrase activity.17

In a fairly recent genetic study, 27 genetic variations of SI were identified in 31 patients who had been diagnosed with CSID. In this study, four of these genetic variations were the most common genetic variations associated with CSID.11 In the model that assumes the population is in Hardy-Weinberg equilibrium, in which the gene that carries the allele for CSID is not evolving and the frequencies of allelic variations stay the same across generations, there is an 83% probability that symptomatic individuals diagnosed with CSID who have European ancestry will have at least one of these four common variations for CSID.11

Additional studies are underway and could help to more accurately determine the prevalence of CSID. It is possible that a significant proportion of affected children and adults are not being tested and therefore are not being diagnosed with CSID. CSID occurs with equal frequency in males and females.

References

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  2. Treem WR. Clinical aspects and treatment congenital sucrase-isomaltase deficiency. J Pediatr Gastroenterol Nutr. 2012;55(suppl 2):S7-13. doi:10.1097/01.mpg.0000421401.57633.90
  3. Alfalah M, Keiser M, Leeb T, et al. Compound heterozygous mutations affect protein folding and function in patients with congenital sucrase-isomaltase deficiency. Gastroenterology. 2009;136(3):883-92. doi:10.1053/j.gastro.2008.11.038
  4. Gericke B, Amiri M, Naim HY. The multiple roles of sucrase-isomaltase in the intestinal physiology. Mol Cell Pediatr. 2016;3(1):2. doi:10.1186/s40348-016-0033-y
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  7. Naim HY, Heine M, Zimmer KP. Congenital sucrase-isomaltase deficiency: heterogeneity of inheritance, trafficking, and function of an intestinal enzyme complex. J Pediatr Gastroenterol Nutr. 2012;55(suppl 2):S13-20. doi: 10.1097/01.mpg.0000421402.57633.4b
  8. Ritz V, Alfalah M, Zimmer KP, et al. Congenital sucrase-isomaltase deficiency because of an accumulation of the mutant enzyme in the endoplasmic reticulum. Gastroenterol. 2003;125(6):1678-85. doi: 10.1053/j.gastro.2003.09.022
  9. Sander P, Alfalah M, Keiser M, et al. Novel mutations in the human sucrase-isomaltase gene (SI) that cause congenital carbohydrate malabsorption. Human Mutat. 2006;27(1):119. doi:10.1002/humu.9392
  10. Spodsberg N, Jacob R, Alfalah M, et al. Molecular basis of aberrant apical protein transport in an intestinal enzyme disorder. J Biol Chem. 2001;276(26):23506-10. doi:10.1074/jbc.C100219200
  11. 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):S34-5. doi: 10.1097/01.mpg.0000421408.65257.b5
  12. Gudman-Høyer E, Fenger HJ, Kern-Hansen P, Madsen PR. Sucrase deficiency in Greenland. Incidence and genetic aspects. Scand J Gastroenterol. 1987;22(1):24-8. doi: 10.3109/00365528708991851
  13. Ellestad-Sayed JJ, Haworth JC, Hildes JA. Disaccharide malabsorption and dietary patterns in two Canadian Eskimo communities. Am J Clin Nutr. 1978;31(8):1473-8. doi: 10.1093/ajcn/31.8.1473
  14. Bell RR, Draper HH, Bergan JG. Sucrose, lactose, and glucose tolerance in northern Alaskan Eskimos. Am J Clin Nutr. 1978;26(11):1185-90. doi: 10.1093/ajcn/26.11.1185
  15. Peterson ML, Herber R. Intestinal sucrase deficiency. Trans Assoc Am Physicians. 1967:80:275-83.
  16. Welsh JD, Poley JR, Bhatia M, Stevenson DE. Intestinal disaccharidase activities in relation to age, race, and mucosal damage. Gastroenterology. 1978;75(5):847-55.
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