Microvillus Inclusion Disease

Microvillus Inclusion Disease

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Microvillus Inclusion Disease is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • Congenital Familial Protracted Diarrhea
  • Congenital Microvillus Atrophy
  • Davidson's Disease
  • Familial Enteropathy, Microvillus

Disorder Subdivisions

  • None

General Discussion

Microvillus inclusion disease is an extremely rare inherited intestinal disorder (enteropathy) that is typically apparent within hours or days after birth. The disorder is characterized by chronic, severe, watery diarrhea and insufficient absorption (malabsorption) of necessary nutrients due to incomplete development (hypoplasia) and/or degeneration (atrophy) of certain cells of the wall of the small intestine (e.g., hypoplastic villus atrophy, defective brush-border assembly and differentiation). In infants with microvillus inclusion disease, chronic diarrhea and malabsorption may result in severe dehydration, deficiency of necessary nutrients (malnutrition), a failure to grow and gain weight at the expected rate (failure to thrive), and/or disturbance of the body's balance of acids and bases, which is essential in regulating the body's composition of bodily fluids (acidosis). Microvillus inclusion disease is inherited as an autosomal recessive genetic trait.

Symptoms

Microvillus inclusion disease is characterized by severe, large amounts of watery diarrhea appearing at birth or within seventy-two hours. Symptoms of a rare late onset form may not occur until two or three months after birth. Diarrhea persists even after oral feeding is stopped and does not decrease with age. Diarrhea often worsens after feeding because of insufficient absorption (malabsorption) of necessary nutrients. The diarrhea often results in life-threatening complications, specifically severe dehydration and metabolic acidosis, which may cause kidney failure, requiring the infant to be hospitalized. There may also be related weight loss, growth retardation and developmental delay.



Infants affected by this disorder require total intravenous hydration and total parenteral nutrition (TPN). TPN may be associated with an increased risk of developing blockage of the liver or bile ducts preventing the normal flow of bile (cholestasis) and liver failure.

Causes

Microvillus inclusion disease is thought to be caused by a basic defect in the cells in the intestinal wall of the small intestine and colon. Some researchers believe that it is inherited as an autosomal recessive trait. The specific genetic mutation involved has not yet been identified.



Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.



All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Affected Populations

Fewer than 100 cases of microvillus inclusion disease had been reported in the medical literature. The true prevalence of this disorder is unknown. Most cases become apparent soon after birth, but it is also believed by some that there is a later-onset form that becomes apparent six to eight weeks after birth in infants that, until then, have appeared healthy. Microvillus inclusion disease affects more females than males with a sex ratio of about 2:1.



Microvillus inclusion disease was first described in the medical literature in 1978.

Standard Therapies

Diagnosis

The diagnosis of microvillus inclusion disease may be based upon electron microscopy of a tissue sample (biopsy) from the intestine of an ailing child, which depicts microscopic findings characteristic of the disorder. Before a biopsy is performed, other causes of dehydration and diarrhea in infants are ruled out.



Treatment

No effective drug treatment is available. Treatment of microvillus inclusion disease is accomplished through intravenous feeding often called total parenteral nutrition (TPN).



However, chronic TPN carries with it high risks of infection (sepsis), liver damage and other organ disorders. Therefore, the affected child must be carefully monitored by a physician.



Some children with severe disease have been treated with transplantation of a part of the small intestine.



Other treatment of microvillus inclusion disease is symptomatic and supportive. Genetic counseling will be of benefit for affected individuals and their families.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.



For information about clinical trials being conducted at the National Institutes of Health (NIH) Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:



Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com

References

TEXTBOOKS

Kennea NL. Microvillus Inclusion Disease. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:351.



Behrman RE, Kliegman RM, Arvin AM., eds. Nelson Textbook of Pediatrics. 15th ed. W.B. Saunder Company. Philadelphia, PA; 1996:1097.



Yamada T, Alpers DH, Owyang C, et al., eds. Textbook of Gastroenterology. 2nd ed. J. B. Lippincott Company. Philadephia, PA; 1995:1669.



REVIEW ARTICLES

Ruemmele FM, Schmitz J, Goulet O. Microvillus inclusion disease (microvillus atrophy). Orphanet J Rare Dis. 2006;1:22.



Sherman PM, Mitchell DJ, Cutz E. Neonatal enteropathies: defining the causes of protracted diarrhea of infancy. J Pediatr Gastroenterol Nutr. 2004;38:16-26.



Mehta DI, Blecker U. Chronic diarrhea in infancy and childhood. J La State Med Soc. 1998;150:419-29.



JOURNAL ARTICLES

Ruemmele FM, Jan D, Lacaille F, et al. New perspectives for children with microvillus inclusion disease: early small bowel transplantation. Transplantation. 2004;77:1024-28.



Goulet O, Ruemmele F, Lacaille F, et al. Irreversible intestinal failure. J Pediatr Gastroenterol Nutr. 2004;38:250-69.



Gambarara M, Diamanti A, Ferretti F, et al. Intractable diarrhea of infancy with congenital intestinal mucosa abnormalities: outcome of four cases. Transplant Proc. 2003;35:3052-53.



Hasegawa T, Sasaki T, Kimura T, et al. Effects of isolated small bowel transplantation on liver dysfunction caused by intestinal failure and long term total parenteral nutrition. Pediatr Transplant. 2002;6:235-39.



Kennea N, Norbury R, Anderson G, et al. Congenital microvillus inclusion disease presenting as antenatal bowel obstruction. Ultrasound Obstet Gynecol. 2001;17:172-74.



Oliva MM, Perman JA, Saavedra JM, et al. Successful intestinal transplantation for microvillus inclusion disease. Gastroenterology. 1994;106:771-74.



FROM THE INTERNET

McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Microvillus Inclusion Disease. Entry Number; 251850: Last Edit Date; 3/17/2004.



Guandalini S, Nocerino A. Congenital Microvillus Atrophy. emedicine. Last Updated: May 25, 2002.

www.emedicine.com/PED/topic461.htm



Greenstein SM, Prowse O. Intestinal Transplantation. emedicine. Last Updated: August 12, 2004.

www.emedicine.com/ped/topic2845/htm



The Salas Laboratory: Epithelial cell polarity and beyond. nd. 3pp.

http://chroma.med.miami.edu/cellbio/Salas/

Resources

March of Dimes Birth Defects Foundation

1275 Mamaroneck Avenue

White Plains, NY 10605

Tel: (914)997-4488

Fax: (914)997-4763

Tel: (888)663-4637

Email: Askus@marchofdimes.com

Internet: http://www.marchofdimes.com



NIH/National Institute of Diabetes, Digestive & Kidney Diseases

Office of Communications & Public Liaison

Bldg 31, Rm 9A06

31 Center Drive, MSC 2560

Bethesda, MD 20892-2560

Tel: (301)496-3583

Email: NDDIC@info.niddk.nih.gov

Internet: http://www2.niddk.nih.gov/



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.

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