Introduction
Tufting enteropathy is an autosomal recessive disease of infancy that leads to severe intestinal failure with electrolyte imbalances and dysfunctional growth. Tufting enteropathy is diagnosed by its key histological features, including crypt hyperplasia, villous atrophy, and focal epithelial tufts consisting of densely packed enterocytes.
What Is Tufting Enteropathy?
Tufting enteropathy is a rare genetic disorder of the intestine that causes intense diarrhea and an inability to absorb nutrients. It starts soon after birth and is a group of disorders called congenital diarrhea. Tufting enteropathy occurs when cells lining the intestine do not develop normally, causing an inability to absorb fluid and nutrients. Children and infants need specialized intravenous nutrition to grow normally and avoid dehydration.
What Is Tufting Enteropathy Also Called?
The synonyms include:
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Intestinal epithelial dysplasia.
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Congenital enteropathy.
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Congenital familial intractable diarrhea with enterocyte assembly abnormalities.
Is Tufting Enteropathy Common?
Tufting enteropathy may be more common than MVA (microvillous atrophy), also called microvillous inclusion disease, common in the Middle East. However, it remains rare. Many cases have not yet been recognized since the disorder is recent. The prevalence is higher in countries with a high degree of consanguinity. Many studies have reported that tufting enteropathy is frequently seen in individuals of middle eastern origin. The prevalence is estimated to be around 150000 to 100000.
What Are the Clinical Aspects of Tufting Enteropathy?
Tufting enteropathy is diagnosed by esophagogastroduodenoscopy, with duodenal histological abnormalities. The tufts are composed of disorganized enterocytes with focal crowding at the basement membrane and villous tips resulting in teardrop configurations. Most affected individuals have secretory diarrhea, and some cases have reported osmotic diarrhea.
Watery diarrhea is abundant in tufting enteropathy cases irrespective of whether the infant is fed or fasted, although fasting improves stool output in some cases. Intractable diarrhea and nutrient malabsorption cause infants to become irritable and develop dehydration and weight loss, which results in impaired growth and failure to thrive. Some individuals may develop vomiting and abdominal distention. Elevated osmolality, quantitative fecal fat, and osmotic gap have been reported.
What Is the Etiopathogenesis of Tufting Enteropathy?
Tufting enteropathy has been associated with an abnormal basement membrane. Basement membrane molecules are responsible for epithelial-mesenchymal cell interactions, instrumental in intestinal differentiation and development. Alterations depict cell-cell and cell-matrix interactions. Tufts correspond to epithelial cells at the villous tips that are not in contact with the basement membrane. A defect in normal enterocyte apoptosis at the end of altered cell-cell interactions is responsible for this effect. The primary or secondary nature still needs to be determined.
What Is the Genetic Association of This Disease?
A clear association between tufting enteropathy and parental consanguinity suggests an autosomal recessive transmission. Genetic counseling may be required on the probable autosomal recessive mode of transmission. The causative gene has not been discovered.
What Is the Cause of Tufting Enteropathy?
The signs of tufting enteropathy usually present within days or hours after birth. But occasionally, the symptoms appear later, around two months after birth, and are less severe. Tufting enteropathy is inherited because of an autosomal recessive genetic trait. This means that both parents should carry a copy of the affected gene to pass the disease on to their progeny.
In some cases, more than one offspring is affected. The causative gene so far has been identified as EpCAM (epithelial cellular adhesion molecule). When children have severe watery diarrhea that does not resolve, they cannot absorb the nutrients they eat, leading to severe complications such as life-threatening dehydration requiring hospitalization. They also have difficulty gaining weight.
What Is the Management of Tufting Enteropathy?
Tufting enteropathy can be life-threatening due to massive diarrhea that causes rapid dehydration and electrolyte imbalance, with subsequent metabolic decomposition within a few days after birth. Diarrhea may persist at a lower level despite bowel rest. The attempts of continuous enteral feeding with a protein hydroxylate or amino acids-based formulas worsen diarrhea, and the newborns develop protein energy malnutrition and rapidly fail to thrive. Individuals have continued on enteral feeding without improvement in diarrhea and severe protein malnutrition.
The same is seen in individuals prescribed immunosuppressive drugs, especially steroids, associated with cyclosporine. Neonatal diarrhea requires permanent parenteral nutrition. There are milder phenotypes than others.
In several cases, the degree of intestinal malabsorption and diarrhea make them dependent on long-term parenteral nutrition, with a risk of complications. Tufting enteropathy causes intestinal malabsorption and diarrhea, making the affected individuals dependent. Intestinal failure may be irreversible. Liver disease may develop into end-stage liver cirrhosis in people with intestinal failure as a result of both underlying digestive disease and unadapted parenteral nutrition.
Management of individuals with intestinal failure requires early recognition of the condition and the analysis of risks. In a few cases, it may be an indication of intestinal transplantation.
The criteria for transplant are under debate regarding vascular thrombosis and sepsis. Life-threatening sepsis may occur only if there is extensive thrombosis.
The poor quality of life might be an indication of intestinal transplantation. The usual criteria include the loss of vascular access, progressive liver disease, and recurring life-threatening sepsis. Parents should be informed about the risks of the procedure.
Conclusion
When long-term parental nutrition is effective and well tolerated, it can opt for a long period without needing intestinal transplantation. The long-term prognosis may be variable. The management should be based on a multidisciplinary approach involving pediatric gastroenterology, nutrition expertise, a nutrition program at home, and a liver transplantation program.
