Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Microvillus Inclusion Disease Workup

  • Author: Stefano Guandalini, MD; Chief Editor: Carmen Cuffari, MD  more...
 
Updated: Jul 17, 2015
 

Laboratory Studies

Measurements of stool electrolytes and osmolality enable rapid and accurate assessment of the pathogenesis of this important chronic diarrhea (osmolar vs secretory) and greatly narrow the differential diagnoses of microvillus inclusion disease.

In assessing the nature of diarrhea, remember that stool samples should be sent for electrolyte and osmolarity measurements only if patients have liquid stools.

Fecal electrolytes demonstrate a typical pattern of secretory diarrhea. Fecal sodium levels are high (approximately 60-120 mEq/L), and no osmotic gap is found. In patients with secretory diarrhea, the following formula applies: 2(Na concentration + K concentration) = stool osmolarity ± 50. In osmotic diarrhea, stool osmolarity exceeds 2(Na concentration + K concentration) by 100 or more.

In osmotic diarrhea, findings on stool microscopy are negative for WBCs, blood (exudative diarrhea), and fat (steatorrhea).

Secretory diarrhea occurs in the fasting state and is associated with large output losses that cause dehydration and metabolic acidosis.

The stool culture is likely negative in prolonged diarrhea, as well as in a diarrhea that lacks blood, a finding that suggests no invasive bacteria.

Serum electrolyte levels may be very useful in the management but add little information to establish a diagnosis.

Cystic fibrosis, the most common cause of pancreatic insufficiency, is best confirmed or ruled out by performing the sweat test.

Next

Other Tests

Findings from duodenal biopsy must not be considered diagnostic. Histologic results of duodenal biopsy samples can range from essentially normal to mildly abnormal, showing the following:

  • Thin mucosa caused by hypoplastic villus atrophy
  • Diffuse villus atrophy (loss of villus height)
  • Crypt hypoplasia

The diagnosis rests on findings demonstrated by electron microscopy (see Histologic Findings).

Rectal biopsy findings demonstrate microvillous involutions and an increased number of secretory granules. This test has been proposed as a relatively easy method for making an early diagnosis.

Previous
Next

Histologic Findings

Electron microscopy demonstrates well-preserved crypt epithelium with abundant microvilli. Villus enterocytes are severely abnormal, particularly toward the apices of the short villi. The microvilli are depleted in number, short, and irregularly arranged. Some of the enterocytes contain the typical microvillus involutions, which are intracellular vacuoles where microvilli are observed lining the inner surface. A striking feature is a number of small, membrane-bound vesicles containing electron-dense material.

A few cases have been described in which the classic microvillous inclusions are shadowed by other features, such as large aggregates of electron lucent, vermiform membranous vesicles in enterocyte cytoplasm.[14, 15]

PAS staining of the intestinal biopsy sample reveals PAS-positive material in the apical cytoplasm. The normal linear staining of the glycocalix is absent. PAS accumulates in low crypts in atypical microvillus atrophy, in upper crypts in congenital microvillus atrophy, and in low villi in late-onset microvillus atrophy.

Anti-CD10 immunohistochemistry shows a marked enlargement of the stained band that appears doubled compared with controls.[16, 17] CD10 is a neutral membrane-associated peptidase; thus, abnormal stain findings with PAS or anti-CD10 immunohistochemistry are expressions of the abnormalities in microvillar structure.

Previous
 
 
Contributor Information and Disclosures
Author

Stefano Guandalini, MD Founder and Medical Director, Celiac Disease Center, Chief, Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Chicago Medical Center; Professor, Department of Pediatrics, Section of Gastroenterology, Hepatology and Nutrition, University of Chicago Division of the Biological Sciences, The Pritzker School of Medicine

Stefano Guandalini, MD is a member of the following medical societies: American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, European Society for Paediatric Gastroenterology, Hepatology & Nutrition, North American Society for the Study of Celiac Disease

Disclosure: Received consulting fee from AbbVie for consulting.

Coauthor(s)

Agostino Nocerino, MD, PhD Chief of Pediatric Oncology, Department of Pediatrics, University of Udine, Italy

Agostino Nocerino, MD, PhD is a member of the following medical societies: American Society of Pediatric Hematology/Oncology, Italian Society of Pediatric Hematology and Oncology, Italian Society of Pediatric Emergency and Urgent Care Medicine, Italian Society of Pediatrics

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Carmen Cuffari, MD Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine

Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, Royal College of Physicians and Surgeons of Canada

Disclosure: Received honoraria from Prometheus Laboratories for speaking and teaching; Received honoraria from Abbott Nutritionals for speaking and teaching.

Additional Contributors

Chris A Liacouras, MD Director of Pediatric Endoscopy, Division of Gastroenterology and Nutrition, Children's Hospital of Philadelphia; Associate Professor of Pediatrics, University of Pennsylvania School of Medicine

Chris A Liacouras, MD is a member of the following medical societies: American Gastroenterological Association

Disclosure: Nothing to disclose.

References
  1. Davidson GP, Cutz E, Hamilton JR, Gall DG. Familial enteropathy: a syndrome of protracted diarrhea from birth, failure to thrive, and hypoplastic villus atrophy. Gastroenterology. 1978 Nov. 75(5):783-90. [Medline].

  2. Reinshagen K, Naim HY, Zimmer KP. Autophagocytosis of the apical membrane in microvillus inclusion disease. Gut. 2002 Oct. 51(4):514-21. [Medline].

  3. Groisman GM, Sabo E, Meir A, Polak-Charcon S. Enterocyte apoptosis and proliferation are increased in microvillous inclusion disease (familial microvillous atrophy). Hum Pathol. 2000 Nov. 31(11):1404-10. [Medline].

  4. Wiegerinck CL, Janecke AR, Schneeberger K, Vogel GF, van Haaften-Visser DY, Escher JC, et al. Loss of Syntaxin 3 Causes Variant Microvillus Inclusion Disease. Gastroenterology. 2014 Apr 8. [Medline].

  5. Al-Daraji WI, Zelger B, Zelger B, Hussein MR. Microvillous inclusion disease: a clinicopathologic study of 17 cases from the UK. Ultrastruct Pathol. 2010 Dec. 34(6):327-32. [Medline].

  6. van der Velde KJ, Dhekne HS, Swertz MA, Sirigu S, Ropars V, Vinke PC. An overview and online registry of microvillus inclusion disease patients and their MYO5B mutations. Hum Mutat. 2013 Dec. 34(12):1597-605. [Medline].

  7. Herzog D, Atkison P, Grant D, et al. Combined bowel-liver transplantation in an infant with microvillous inclusion disease. J Pediatr Gastroenterol Nutr. 1996 May. 22(4):405-8. [Medline].

  8. Oliva MM, Perman JA, Saavedra JM, et al. Successful intestinal transplantation for microvillus inclusion disease. Gastroenterology. 1994 Mar. 106(3):771-4. [Medline].

  9. Ruemmele FM, Jan D, Lacaille F, et al. New perspectives for children with microvillous inclusion disease: early small bowel transplantation. Transplantation. 2004 Apr 15. 77(7):1024-8. [Medline].

  10. Kennea N, Norbury R, Anderson G, Tekay A. Congenital microvillous inclusion disease presenting as antenatal bowel obstruction. Ultrasound Obstet Gynecol. 2001 Feb. 17(2):172-4. [Medline].

  11. Chen CP, Su YN, Chern SR, Wu PC, Wang W. Prenatal diagnosis of microvillus inclusion disease. Taiwan J Obstet Gynecol. 2011 Sep. 50(3):399-400. [Medline].

  12. Ruemmele FM, Schmitz J, Goulet O. Microvillous inclusion disease (microvillous atrophy). Orphanet J Rare Dis. 2006 Jun 26. 1:22. [Medline].

  13. Burgis JC, Pratt CA, Higgins JP, Kerner JA. Multiple hepatic adenomas in a child with microvillus inclusion disease. Dig Dis Sci. 2013 Oct. 58(10):2784-8. [Medline].

  14. Weeks DA, Zuppan CW, Malott RL, Mierau GW. Microvillous inclusion disease with abundant vermiform, electron-lucent vesicles. Ultrastruct Pathol. 2003 Sep-Oct. 27(5):337-40. [Medline].

  15. Iancu TC, Mahajnah M, Manov I, Shaoul R. Microvillous inclusion disease: ultrastructural variability. Ultrastruct Pathol. 2007 May-Jun. 31(3):173-88. [Medline].

  16. Groisman GM, Amar M, Livne E. CD10: a valuable tool for the light microscopic diagnosis of microvillous inclusion disease (familial microvillous atrophy). Am J Surg Pathol. 2002 Jul. 26(7):902-7. [Medline].

  17. Youssef N, M Ruemmele F, Goulet O, Patey N. [CD10 expression in a case of microvillous inclusion disease]. Ann Pathol. 2004 Dec. 24(6):624-7. [Medline].

  18. Halac U, Lacaille F, Joly F, Hugot JP, Talbotec C, Colomb V, et al. Microvillous inclusion disease: how to improve the prognosis of a severe congenital enterocyte disorder. J Pediatr Gastroenterol Nutr. 2011 Apr. 52(4):460-5. [Medline].

  19. Phillips AD, Schmitz J. Familial microvillous atrophy: a clinicopathological survey of 23 cases. J Pediatr Gastroenterol Nutr. 1992 May. 14(4):380-96. [Medline].

  20. Assmann B, Hoffmann GF, Wagner L, et al. Dihydropyrimidinase deficiency and congenital microvillous atrophy: coincidence or genetic relation?. J Inherit Metab Dis. 1997 Sep. 20(5):681-8. [Medline].

  21. Carruthers L, Dourmashkin R, Phillips A. Disorders of the cytoskeleton of the enterocyte. Clin Gastroenterol. 1986 Jan. 15(1):105-20. [Medline].

  22. Cutz E, Rhoads JM, Drumm B, et al. Microvillus inclusion disease: an inherited defect of brush-border assembly and differentiation. N Engl J Med. 1989 Mar 9. 320(10):646-51. [Medline].

  23. Michail S, Collins JF, Xu H, et al. Abnormal expression of brush-border membrane transporters in the duodenal mucosa of two patients with microvillus inclusion disease. J Pediatr Gastroenterol Nutr. 1998 Nov. 27(5):536-42. [Medline].

  24. Nathavitharana KA, Green NJ, Raafat F, Booth IW. Siblings with microvillous inclusion disease. Arch Dis Child. 1994 Jul. 71(1):71-3. [Medline].

  25. Pecache N, Patole S, Hagan R, et al. Neonatal congenital microvillus atrophy. Postgrad Med J. 2004 Feb. 80(940):80-3. [Medline].

  26. Phillips AD, Brown A, Hicks S, et al. Acetylated sialic acid residues and blood group antigens localise within the epithelium in microvillous atrophy indicating internal accumulation of the glycocalyx. Gut. 2004 Dec. 53(12):1764-71. [Medline].

  27. Phillips AD, Jenkins P, Raafat F, Walker-Smith JA. Congenital microvillous atrophy: specific diagnostic features. Arch Dis Child. 1985 Feb. 60(2):135-40. [Medline].

  28. Phillips AD, Szafranski M, Man LY, Wall WJ. Periodic acid-Schiff staining abnormality in microvillous atrophy: photometric and ultrastructural studies. J Pediatr Gastroenterol Nutr. 2000 Jan. 30(1):34-42. [Medline].

 
Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.