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EPCAM-associated congenital tufting enteropathy

Tuesday 31 May 2005

Definition: Intestinal epithelial dysplasia (IED), also known as tufting enteropathy, is a congenital enteropathy presenting with early-onset severe intractable diarrhea causing sometimes irreversible intestinal failure.

To date, no epidemiological data are available, however, the prevalence can be estimated at around 1/50,000-100,000 live births in Western Europe.

The prevalence seems higher in areas with high degree of consanguinity and in patients of Arabic origin.

Infants develop within the first days after birth a watery diarrhea persistent in spite of bowel rest and parenteral nutrition. Some infants are reported to have associated choanal rectal or esophageal atresia.

IED is thought to be related to abnormal enterocytes development and/or differentiation. Nonspecific punctuated keratitis was reported in more than 60% of patients.

Histology shows various degree of villous atrophy, with low or without mononuclear cell infiltration of the lamina propria but specific histological abnormalities involving the epithelium with disorganization of surface enterocytes with focal crowding, resembling tufts.

Several associated specific features were reported, including abnormal deposition of laminin and heparan sulfate proteoglycan (HSPG) in the basement membrane, increased expression of desmoglein and ultrastructural changes in the desmosomes, and abnormal distribution of alpha2beta1 integrin adhesion molecules.

One model of transgenic mice in which the gene encoding the transcription factor Elf3 is disrupted have morphologic features resembling IED.

Parental consanguinity and/or affected siblings suggest an autosomal recessive transmission but the causative gene(s) have not been yet identified making prenatal diagnosis unavailable.

Some infants have a milder phenotype than others but in most patients, the severity of the intestinal malabsorption even with enteral feeding make them totally dependent on daily long-term parenteral nutrition with a subsequent risk of complications.

IED becomes an indication for intestinal transplantation, while timing of referral for it is crucial before the onset of severe complications.

Etiology

- EPCAM germline mutations

See also

- neontal enteropathy (intractable diarrhea of infancy)

  • microvillous inclusion disease

- EPCAM
- SPINT2-associated congenital tufting enteropathy
- tufting enteropahty and chronic arthritis

Refererences

- Further evidence for EpCAM as the gene for congenital tufting enteropathy. Sivagnanam M, Schaible T, Szigeti R, Byrd RH, Finegold MJ, Ranganathan S, Gopalakrishna GS, Tatevian N, Kellermayer R. Am J Med Genet A. 2010 Jan;152A(1):222-4. PMID: 20034091

- Al-Mayouf, S. M.; Alswaied, N.; Alkuraya, F. S.; AlMehaidib, A.; Faqih, M. : Tufting enteropahty and chronic arthritis: a newly recognized association with a novel EpCAM gene mutation. J. Pediat. Gastroent. Nutr. 49: 642-644, 2009. PubMed ID : 19820410

- Expression of EpCam and villin in Barrett’s esophagus and in gastric cardia. Anders M, Sarbia M, Grotzinger C, Meining A, Hofler H, Wiedenmann B, Rosch T. Dis Markers. 2008;24(6):287-92. PMID: 18688077

- Identification of EpCAM as the gene for congenital tufting enteropathy. Sivagnanam M, Mueller JL, Lee H, Chen Z, Nelson SF, Turner D, Zlotkin SH, Pencharz PB, Ngan BY, Libiger O, Schork NJ, Lavine JE, Taylor S, Newbury RO, Kolodner RD, Hoffman HM. Gastroenterology. 2008 Aug;135(2):429-37. Epub 2008 May 15. PMID: 18572020

- Identification of EpCAM as the gene for congenital tufting enteropathy. Sivagnanam M, Mueller JL, Lee H, Chen Z, Nelson SF, Turner D, Zlotkin SH, Pencharz PB, Ngan BY, Libiger O, Schork NJ, Lavine JE, Taylor S, Newbury RO, Kolodner RD, Hoffman HM. Gastroenterology. 2008 Aug;135(2):429-37. PMID: 18572020

- Intestinal epithelial dysplasia (tufting enteropathy). Goulet O, Salomon J, Ruemmele F, de Serres NP, Brousse N. Orphanet J Rare Dis. 2007 Apr 20;2:20. PMID: 17448233

- Patey N, Scoazec JY, Cuenod-Jabri B, Canioni D, Kedinger M, Goulet O, Brousse N. Distribution of cell adhesion molecules in infants with intestinal epithelial dysplasia (tufting enteropathy). Gastroenterology. 1997 Sep;113(3):833-43. PMID: 9287975

- Reifen RM, Cutz E, Griffiths AM, Ngan BY, Sherman PM. Tufting enteropathy: a newly recognized clinicopathological entity associated with refractory diarrhea in infants. J Pediatr Gastroenterol Nutr. 1994 Apr;18(3):379-85. PMID: 8057225