''Congenital tufting enteropathy'' is an inherited disorder of the small intestine that presents with intractable diarrhea in young children.

Signs and symptoms

The infants present in the first few days of life with watery diarrhoea. This leads rapidly to dehydration and electrolyte imbalance and metabolic decompensation. Enteral feeding with a protein hydrolysate or amino acid based formulas worsen the diarrhoea and the children rapidly fail to thrive and develop protein energy malnutrition. In the majority of cases the severity of the malabsorption and diarrhoea make them dependent on daily long term total parenteral nutrition. Hepatic fibrosis and

cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, chronic liver failure or chronic hepatic failure and end-stage liver disease, is a chronic condition of the liver in which the normal functioning tissue, or parenchyma, is replaced ...

are known complications.

Associated conditions

*Choanal atresia *Nonspecific punctuated keratitis (60%) *Oesophageal atresia *Unperforated anus

Genetics

Two genes have been associated with this condition:

Epithelial cell adhesion molecule Epithelial cell adhesion molecule (EpCAM), also known as CD326 among other names, is a transmembrane glycoprotein mediating Ca2+-independent homotypic cell–cell adhesion in epithelia. EpCAM is also involved in cell signaling, migration, pro ...

(EpCAM) on

chromosome 2 Chromosome 2 is one of the twenty-three pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 2 is the second-largest human chromosome, spanning more than 242 million base pairs and representing almost ei ...

(2p21) and

SPINT2 Kunitz-type protease inhibitor 2 is an enzyme inhibitor that in humans is encoded by the ''SPINT2'' gene. SPINT2 is a transmembrane protein with two extracellular Kunitz domains to inhibit serine proteases. This gene is a presumed tumor suppressor ...

chromosome 19 Chromosome 19 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 19 spans more than 61.7 million base pairs, the building material of DNA. It is considered the most Gene density, gene-ri ...

. SPINT2 is a Kunitz-type

protease A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalysis, catalyzes proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products ...

inhibitor. The mutation in the EpCAM gene in Kuwait and Qatar appears to have originated 5000–6000 years ago.

Pathology

Histological examination of the small bowel shows varying degrees of villous atrophy, with low or without

mononuclear cell infiltration In immunology, agranulocytes (also known as nongranulocytes or mononuclear leukocytes) are one of the two types of leukocytes (white blood cells), the other type being granulocytes. Agranular cells are noted by the absence of Granule (cell biol ...

of the

lamina propria The lamina propria is a thin layer of connective tissue that forms part of the moist linings known as mucous membranes or mucosae, which line various tubes in the body, such as the respiratory tract, the gastrointestinal tract, and the urogenital ...

. The most important feature involves the epithelium where the surface enterocytes are disorganized with focal crowding creating structures resembling tufts. Other features that have been reported include the abnormal deposition of

laminin Laminins are a family of glycoproteins of the extracellular matrix of all animals. They are major constituents of the basement membrane, namely the basal lamina (the protein network foundation for most cells and organs). Laminins are vital to bi ...

and

heparan sulfate proteoglycan Heparan sulfate (HS) is a linear polysaccharide found in all animal tissues. It occurs in a proteoglycan (HSPG, i.e. Heparan Sulfate ProteoGlycan) in which two or three HS chains are attached in close proximity to cell surface or extracellular ma ...

within the basement membrane and increased expression of

desmoglein The desmogleins are a family of desmosomal cadherins consisting of proteins DSG1, DSG2, DSG3, and DSG4. They play a role in the formation of desmosomes that join cells to one another. Pathology Desmogleins are targeted in the autoimmune disease ...

. Electron microscopic changes in the desmosomes have been noted as have abnormal distribution of alpha2beta1 integrin adhesion molecules.

Diagnosis

Differential diagnosis

* Congenital chloride diarrhoea * Congenital sodium diarrhoea * Familial microvillous atrophy *

Glucose-galactose malabsorption Glucose-galactose malabsorption is a rare condition in which the cells lining the intestine cannot take in the sugars glucose and galactose, which prevents proper digestion of these molecules and larger molecules made from them. Glucose and galact ...

Management

Bowel transplantation may be an option.

Epidemiology

The prevalence of this disorder has been estimated to be 1/50,000-100,000 per live births in Western Europe. It appears to be higher in areas with high degree of consanguinity and in patients of Arabic origin.

History

The first cases appears to have been reported in 1978 by Davidson et al.. These authors reported a five cases of intractable diarrhoea four of whom died. Post mortum showed a thin and dilated intestine with flat small bowel mucosa. A number of jejunal biopsies had been taken during life and these showed partial villous atrophy with by crypt hyperplasia and an increased number of mitotic figures in the crypts. Normal numbers and types of mononuclear cells were present in the lamina propria. Most notably focal epithelial tufts were found on the surface epithelium. These tufts were composed of closely packed enterocytes with apical rounding of the plasma membrane, resulting in a teardrop configuration of the cells. Inclusion bodies or secretory granules were not visualised on transmission electron microscopy within the cytoplasm of the villous enterocytes. Reifen ''et al'' reported 2 additional cases in 1994 and coined the name congenital tufting enteropathy.

References

{{reflist Diseases of intestines