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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.


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.


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.

Contributor Information and Disclosures

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.


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.

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