Diarrhea pp 159-175 | Cite as

Congenital Disorders of Digestion and Absorption

  • Douglas Mogul
  • Eric Sibley
Chapter
First Online:
Part of the Clinical Gastroenterology book series (CG)

Summary

Disorders of digestion and/or absorption of any of the major nutrient forms (carbohydrates, proteins, and lipids) can result in clinical symptoms of diarrhea or steatorrhea. Congenital and heritable genetic conditions associated with nutrient maldigestion and malabsorption are described below. A classification of such disorders, their genetic bases, and their clinical manifestations is presented in Table 9.1.

Key Words

Congenital diarrhea Glucose–galactose malabsorption Lactase deficiency Sucrase–isomaltase deficiency Adult-type hypolactasia Fructose malabsorption Fanconi–Bickel syndrome Enterokinase deficiency Trypsinogen deficiency Lysinuric protein intolerance Abetalipoproteinemia Hypobetalipoproteinemia Chylomicron retention disease Primary bile acid malabsorption Enteric anendocrinosis Congenital zinc deficiency 
This is a preview of subscription content, log in to check access.

References

  1. 1.
    Levin B, Abraham JM, Burgess EA, Wallis PG. Congenital lactose malabsorption. Arch Dis Child 1970; 45:173–177.PubMedCrossRefGoogle Scholar
  2. 2.
    Savilahti E, Launiala K, Kuitunen P. Congenital lactase deficiency: a clinical study on 16 patients. Arch Dis Child 1983; 58:246–252.PubMedCrossRefGoogle Scholar
  3. 3.
    Jarvela I, Enattah NS, Kokkonen J, Varilo T, Savilahti E, Peltonen L. Assignment of the locus for congenital lactase deficiency to 2q21, in the vicinity of but separate from the lactase–phlorizin hydrolase gene. Am J Hum Genet 1998; 63: 1078–1085.PubMedCrossRefGoogle Scholar
  4. 4.
    Kuokkanen M, Kokkonen J, Enattah NS, Ylisaukko-oja T, Komu H, Varilo T, Peltonen L, Savilahti E, Jarvela I. Mutations in the translated region of the lactase gene (LCT) underlie congenital lactase deficiency. Am J Hum Genet 2006; 78:339–344.PubMedCrossRefGoogle Scholar
  5. 5.
    Romagnuolo J, Schiller D, Bailey RJ. Using breath tests wisely in a gastroenterology practice: an evidence-based review of indications and pitfalls in interpretation. Am J Gastroenter 2002 May; 97(5):1113–1126.CrossRefGoogle Scholar
  6. 6.
    Bedine MS, Bayless TM. Intolerance of small amounts of lactose by individuals with low lactase levels. Gastroenterology 1973 Nov; 65(5):735–743.PubMedGoogle Scholar
  7. 7.
    Forget P, Lombet J, Grandfils C, Dandrifosse G, Geubelle F. Lactase insufficiency revisited. J Pediatr Gastroenterol Nutr 1985 Dec; 4(6):868–872.PubMedCrossRefGoogle Scholar
  8. 8.
    Birge SJ Jr, Keutmann HT, Cuatrecasas P, Whedon GD. Osteoporosis, intestinal lactase deficiency and low dietary calcium intake. N Engl J Med 1967 Feb 23; 276(8):445–448.PubMedCrossRefGoogle Scholar
  9. 9.
    Naim HY, Roth J, Sterchi EE, Lentze M, Milla P, Schmitz J, Hauri HP. Sucrase–isomaltase deficiency in humans. Different mutations disrupt intracellular transport, processing, and function of an intestinal brush border enzyme. J Clin Invest 1988 Aug; 82(2):667–679.PubMedCrossRefGoogle Scholar
  10. 10.
    Treem WR. Congenital sucrase–isomaltase deficiency. J Pediatr Gastroenterol Nutr 1995 Jul; 21(1):1–14.PubMedCrossRefGoogle Scholar
  11. 11.
    Gudmand-Høyer E, Fenger HJ, Kern-Hansen P, Madsen PR. Sucrase deficiency in Greenland. Incidence and genetic aspects. Scand J Gastroenterol 1987 Jan; 22(1):24–28.PubMedCrossRefGoogle Scholar
  12. 12.
    Treem WR, McAdams L, Stanford L, Kastoff G, Justinich C, Hyams J. Sacrosidase therapy for congenital sucrase–isomaltase deficiency. J Pediatr Gastroenterol Nutr 1999 Feb; 28(2):137–142.PubMedCrossRefGoogle Scholar
  13. 13.
    Wright EM, Loo DD, Panayotova-Heiermann M, Lostao MP, Hirayama BH, Mackenzie B, Boorer K, Zampighi G. ‘Active’ sugar transport in eukaryotes. J Exp Biol 1994 Nov; 196:197–212.PubMedGoogle Scholar
  14. 14.
    Hediger MA, Budarf ML, Emanuel BS, Mohandas TK, Wright EM. Assignment of the human intestinal Na+/glucose cotransporter gene (SGLT1) to the q11.2-qter region of chromosome 22. Genomics 1989 Apr; 4(3):297–300.PubMedCrossRefGoogle Scholar
  15. 15.
    Barnes G, McKellar W, Lawrance S. Detection of fructose malabsorption by breath hydrogen test in a child with diarrhea. J Pediatr 1983 Oct; 103(4):575–577.PubMedCrossRefGoogle Scholar
  16. 16.
    Burant CF, Takeda J, Brot-Laroche E, Bell GI, Davidson NO. Fructose transporter in human spermatozoa and small intestine is GLUT5. J Biol Chem 1992 Jul 25; 267(21):14523–14526.PubMedGoogle Scholar
  17. 17.
    Davidson NO, Hausman AM, Ifkovits CA, Buse JB, Gould GW, Burant CF, Bell GI. Human intestinal glucose transporter expression and localization of GLUT5. Am J Physiol 1992 Mar; 262(3 Pt 1):C795–C800.PubMedGoogle Scholar
  18. 18.
    Li Q, Manolescu A, Ritzel M, Yao S, Slugoski M, Young JD, Chen XZ, Cheeseman CI. Cloning and functional characterization of the human GLUT7 isoform SLC2A7 from the small intestine. Am J Physiol Gastrointest Liver Physiol 2004 Jul; 287(1):G236–G242. Epub 2004 Mar 19.PubMedCrossRefGoogle Scholar
  19. 19.
    Kellett GL, Brot-Laroche E. Apical GLUT2: a major pathway of intestinal sugar absorption. Diabetes 2005 Oct; 54(10):3056–3062.PubMedCrossRefGoogle Scholar
  20. 20.
    Manz F, Bickel H, Brodehl J, Feist D, Gellissen K, Geschöll-Bauer B, Gilli G, Harms E, Helwig H, Nützenadel W, et al. Fanconi–Bickel syndrome. Pediatr Nephrol 1987 Jul; 1(3):509–518.PubMedCrossRefGoogle Scholar
  21. 21.
    Mueckler M, Kruse M, Strube M, Riggs AC, Chiu KC, Permutt MA. A mutation in the Glut2 glucose transporter gene of a diabetic patient abolishes transport activity. J Biol Chem 1994 Jul 8; 269(27):17765–17767.PubMedGoogle Scholar
  22. 22.
    Santer R, Schneppenheim R, Dombrowski A, Götze H, Steinmann B, Schaub J. Mutations in GLUT2, the gene for the liver-type glucose transporter, in patients with Fanconi–Bickel syndrome. Nat Genet 1997 Nov; 17(3):324–326.PubMedCrossRefGoogle Scholar
  23. 23.
    Holzinger A, Maier EM, Bück C, Mayerhofer PU, Kappler M, Haworth JC, Moroz SP, Hadorn HB, Sadler JE, Roscher AA. Mutations in the proenteropeptidase gene are the molecular cause of congenital enteropeptidase deficiency. Am J Hum Genet 2002 Jan; 70(1):20–25.PubMedCrossRefGoogle Scholar
  24. 24.
    Férec C, Raguénès O, Salomon R, Roche C, Bernard JP, Guillot M, Quéré I, Faure C, Mercier B, Audrézet MP, Guillausseau PJ, Dupont C, Munnich A, Bignon JD, Le Bodic L. Mutations in the cationic trypsinogen gene and evidence for genetic heterogeneity in hereditary pancreatitis. J Med Genet 1999 Mar; 36(3): 228–232.PubMedGoogle Scholar
  25. 25.
    Sahin-Toth M, Graf L, Toth M. Trypsinogen stabilization by mutation arg117-to-his: a unifying pathomechanism for hereditary pancreatitis? Biochem Biophys Res Commun 1999; 264:505–508.PubMedCrossRefGoogle Scholar
  26. 26.
    Whitcomb DC, Gorry MC, Preston RA, Furey W, Sossenheimer MJ, Ulrich CD, Martin SP, Gates LK Jr, Amann ST, Toskes PP, Liddle R, McGrath K, Uomo G, Post JC., Ehrlich GD. Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene. Nat Genet 1996; 14:141–145.PubMedCrossRefGoogle Scholar
  27. 27.
    Parto K, Kallajoki M, Aho H, Simell O. Pulmonary alveolar proteinosis and glomerulonephritis in lysinuric protein intolerance: case reports and autopsy findings of four pediatric patients. Hum Pathol 1994; 25:400–407.PubMedCrossRefGoogle Scholar
  28. 28.
    McManus DT, Moore R, Hill CM, Rodgers C, Carson DJ, Love AHG. Necropsy findings in lysinuric protein intolerance. J Clin Pathol 1996; 49:345–347.PubMedCrossRefGoogle Scholar
  29. 29.
    Raabe M, Flynn LM, Zlot CH, Wong JS, Veniant MM, Hamilton RL, Young SG. Knockout of the abetalipoproteinemia gene in mice: reduced lipoprotein secretion in heterozygotes and embryonic lethality in homozygotes. Proc Natl Acad Sci 1998; 95:8686–8691.PubMedCrossRefGoogle Scholar
  30. 30.
    Martin MG. Congenital intestinal transport defects. In: Kleinman RE, et al., eds. Walker’s pediatric gastrointestinal disease, 5th ed. Hamilton, BC Decker, pp. 289–308.Google Scholar
  31. 31.
    Roy CC, Levy E, Green PH, Sniderman A, Letarte J, Buts JP, Orquin J, Brochu P, Weber AM, Morin CL, et al. Malabsorption, hypocholesterolemia, and fat-filled enterocytes with increased intestinal apoprotein B. Chylomicron retention disease. Gastroenterology 1987 Feb; 92(2):390–399.PubMedGoogle Scholar
  32. 32.
    Schekman R, Orci L. Coat proteins and vesicle budding. Science 1996 Mar 15; 271(5255):1526–1533.PubMedCrossRefGoogle Scholar
  33. 33.
    Heubi JE, Balistreri WF, Fondacaro JD, Partin JC, Schubert WK. Primary bile acid malabsorption: defective in vitro ileal active bile acid transport. Gastroenterology 1982 Oct; 83(4):804–811.PubMedGoogle Scholar
  34. 34.
    Wong MH, Rao PN, Pettenati MJ, Dawson PA. Localization of the ileal sodium–bile acid cotransporter gene (SLC10A2) to human chromosome 13q33. Genomics 1996 May 1; 33(3):538–540.PubMedCrossRefGoogle Scholar
  35. 35.
    Wang J, Cortina G, Wu SV, Tran R, Cho JH, Tsai MJ, Bailey TJ, Jamrich M, Ament ME, Treem WR, Hill ID, Vargas JH, Gershman G, Farmer DG, Reyen L, Martín MG. Mutant neurogenin-3 in congenital malabsorptive diarrhea. N Engl J Med 2006 Jul 20; 355(3):270–280.PubMedCrossRefGoogle Scholar
  36. 36.
    Cortina G, Smart CN, Farmer DG, Bhuta S, Treem WR, Hill ID, Martín MG. Enteroendocrine cell dysgenesis and malabsorption, a histopathologic and immunohistochemical characterization. Hum Pathol 2007 Apr; 38(4):570–580.PubMedCrossRefGoogle Scholar
  37. 37.
    Küry S, Dréno B, Bézieau S, Giraudet S, Kharfi M, Kamoun R, Moisan JP. Identification of SLC39A4, a gene involved in acrodermatitis enteropathica. Nat Genet 2002 Jul; 31(3):239–240.PubMedCrossRefGoogle Scholar
  38. 38.
    Dufner-Beattie J, Wang F, Kuo YM, Gitschier J, Eide D, Andrews GK. The acrodermatitis enteropathica gene ZIP4 encodes a tissue-specific, zinc-regulated zinc transporter in mice. J Biol Chem 2003 Aug 29; 278(35):33474–33481.PubMedCrossRefGoogle Scholar
  39. 39.
    Van Wouwe JP. Clinical and laboratory diagnosis of acrodermatitis enteropathica. Eur J Pediatr 1989 Oct; 149(1):2–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Douglas Mogul
    • 1
  • Eric Sibley
    • 2
  1. 1.John Hopkins University School of MedicineBaltimoreUSA
  2. 2.Department of Pediatrics, Division of Gastroenterology, Hepatology and NutritionStanford University Medical School of MedicineStanfordUSA

Personalised recommendations