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What Is Microvillus Inclusion Disease?
Microvillus inclusion disease was first described in the medical literature in 1978. It is an extremely rare condition characterized by chronic, watery, life-threatening diarrhea typically starting in the first hours to days of life. Rarely, diarrhea begins around age three or four months, and food intake increases the diarrhea frequency. Microvillus inclusion disease is also known by other names like congenital enteropathy, congenital microvillous atrophy, Davidson disease, protracted familial enteropathy, intractable diarrhea of infancy, and microvillous atrophy. Several genes have been detected that are believed to be involved in microvillus inclusion disease. Infants and children with this disease often require total intravenous hydration and parenteral nutrition (TPN) to avoid dehydration and normal growth.
What Are the Signs and Symptoms of Microvillus Inclusion Disease?
Microvillus inclusion disease is characterized by chronic, large amounts of watery diarrhea during the first hours to days of life. Symptoms of a rare late-onset type may not appear until two or three months after birth. Diarrhea continues even after oral feeding is stopped and does not subside with age. It often worsens after oral feeding because of the malabsorption of necessary nutrients. Diarrhea usually results in life-threatening complications, especially severe dehydration, and metabolic acidosis, which may lead to kidney failure and require the individual to be hospitalized. There may also be related growth retardation, weight loss, and developmental delay. Infants affected by this disease need total intravenous hydration and parenteral nutrition (TPN). TPN may be associated with an increased chance of developing liver blockage or interruption in the flow of bile caused by an obstruction in the bile ducts (cholestasis) and liver failure. Cholestasis and liver disease can also happen independently of TPN because of the genetic defect in the ductal cells of the bile.
What Causes Microvillus Inclusion Disease?
Microvillus inclusion disease is mainly caused by loss of function changes (mutations) in the myosin Vb (Myo5b) gene, a molecular motor gene responsible for the traffic of proteins into the brush border of epithelial cells. Mutations cause most cases of microvillus inclusion disease in the Myo5b gene. However, some individuals with this condition with late presentation and milder disease can have mutations in the syntaxin 3 (a gene for a SNARE protein) that aids in vesicle fusion with the membrane.
Microvillus inclusion disease follows an autosomal recessive pattern of inheritance which means that a gene carries the disease on a chromosome that is not involved in determining an individual's sex. Both genders can be affected, although it appears more often in women. Because this gene is recessive, both parents must carry it to pass the disease on to their children. In some families, more than one infant or child is affected.
Each individual carries a few abnormal genes. Parents with the same ancestry or descent (consanguineous) have a greater chance than unrelated parents carrying the same abnormal gene, increasing the risk of having children with a recessive genetic disease. Microvillus inclusion disease has been documented in consanguineous families.
How Common Is Microvillus Inclusion Disease?
The true prevalence of microvillus inclusion disease is still unknown. However, less than 100 cases of this condition have been reported in the medical literature. Most cases become evident soon after birth, but experts believe that a later-onset form becomes apparent six to eight weeks after the birth in infants and, until then, they appear healthy. The condition typically affects more females than males, with a ratio of about 2:1.
How Is Microvillus Inclusion Disease Diagnosed?
Detecting microvillus inclusion disease involves several steps. First, healthcare providers determine the kind of diarrhea involved and which nutrients cannot be absorbed.
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Electron Microscopy Procedure: If the provider suspects congenital diarrhea, the provider performs electron microscopy of a tiny tissue sample (biopsy) from the affected intestine to confirm the diagnosis. This procedure usually takes a couple of minutes and is painless. Using electron microscopy, providers can identify the main features of microvillus inclusion disease, which are tiny but distinct differences in the small intestine cells. Providers usually use a flexible viewing tube called an endoscope to take a small sample. The endoscope is swallowed through the mouth and into the stomach. Using electron microscopy, providers can identify the main features of microvillus inclusion disease.
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Genetic Testing: This can be done to see whether gene differences cause microvillus inclusion disease and other congenital diarrheas. Before a biopsy is performed, other possible causes of dehydration and diarrhea in infants are ruled out.
How Is Microvillus Inclusion Disease Treated?
Currently, no effective drug treatment exists. Different drugs have been tried to stop severe diarrhea, but none have proven effective. So instead, the condition is treated through intravenous feeding called total parenteral nutrition (TPN) to get enough nutrition. TPN can help stabilize an infant's health, but usually, it is not a good long-term solution. However, chronic TPN causes high risks of sepsis, liver damage, and other organ disorders over time. Therefore, the affected infant must be carefully monitored by a healthcare provider. When TPN causes these complications, intestinal transplantation is often the best option. Some children with severe diseases have been successfully treated by transplanting a part of the small intestine. Other treatment options are symptomatic and supportive care. Genetic counseling is suggested for affected individuals and their families. Individuals with a family history of microvillus inclusion disease can aid from genetic counseling when they start to plan for children.
Conclusion
Microvillus inclusion disease is a rare genetic intestinal disorder marked by chronic, watery, life-threatening diarrhea typically starting in the first hours to days of life. This disease is inherited in the form of an autosomal recessive genetic trait, meaning both parents must carry a copy of the affected gene to pass the disease on to their child. There are currently no drug treatments for microvillus inclusion disease. Instead, treatment is supportive and involves long-term maintenance of nutrition and hydration with TPN. However, TPN may increase the risk of infections and liver damage over time.
