NORD gratefully acknowledges Nadia Ameen, MD, Professor Pediatrics, Cellular and Molecular Physiology, Yale University School Medicine, for assistance in the preparation of this report.
Microvillus inclusion disease (MVID) 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 surface cells of the wall of the small intestine (e.g., hypoplastic villus atrophy, defective brush-border assembly and differentiation). Infants with MVID may have 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). MVID is inherited in an autosomal recessive pattern.
MVID was first described in the medical literature in 1978.
MVID 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 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. Liver disease and cholestatis can also occur independent of TPN due to the genetic defect in bile duct cells.
MVID is caused by loss of function changes (mutations) in myosin Vb (Myo5b) gene, a molecular motor gene that is responsible for traffic of proteins into the brush border of epithelial cells. Most cases of MVID are caused by mutations in Myo5b. However, some patients with MVID with late presentation and milder disease have been reported to have mutations in syntaxin 3, a gene for a SNARE protein that is responsible for vesicle fusion with the membrane.
MVID follows an autosomal recessive pattern of inheritance. Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working 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 non-working 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 working genes from both parents 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. MVID has been reported in consanguineous families.
Fewer than 100 cases of MVID have 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. MVID affects more females than males with a sex ratio of about 2:1.
The diagnosis of MVID may be based upon electron microscopy of a tissue sample (biopsy) from the intestine of an ailing child, which depicts microscopic findings of brush border defects in the villus in association with microvillus inclusions (MIs) usually in villus enterocytes characteristic of the disorder. Genetic testing is available and can confirm the diagnosis. Before a biopsy is performed, other causes of dehydration and diarrhea in infants are ruled out.
No effective drug treatment is available. Treatment of MVID is accomplished through intravenous feeding 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 is symptomatic and supportive. Genetic counseling is recommended for affected individuals and their families.
Recent studies have identified kinase drug targets that await development based on defects in kinase signaling pathways in MVID.
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 web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website: https://rarediseases.org/for-patients-and-families/information-resources/info-clinical-trials-and-research-studies/
For information about clinical trials sponsored by private sources, contact: www.centerwatch.com
For more information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
For more information about MVID, contact:
Ameen Laboratory-Yale University School of Medicine
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