MCID: DRR003
MIFTS: 37

Diarrhea 5, with Tufting Enteropathy, Congenital

Categories: Genetic diseases, Rare diseases, Gastrointestinal diseases

Aliases & Classifications for Diarrhea 5, with Tufting Enteropathy, Congenital

MalaCards integrated aliases for Diarrhea 5, with Tufting Enteropathy, Congenital:

Name: Diarrhea 5, with Tufting Enteropathy, Congenital 57 75 29 13 6 73
Congenital Tufting Enteropathy 12 59 75
Diar5 57 12 75
Cte 57 75 3
Congenital Diarrhea 5 with Tufting Enteropathy 12 15
Intestinal Epithelial Cell Dysplasia 57 75
Intestinal Epithelial Dysplasia 53 59
Tufting Enteropathy 12 53
Ied 53 59
Congenital Familial Intractable Diarrhea with Epithelial or Epithelium Abnormalities 12
Congenital Familial Intractable Diarrhea with Enterocytes Assembly Abnormalities 53
Diarrhea, Type 5, with Tufting Enteropathy, Congenital 40
Enteropathy, Congenital Tufting; Cte 57
Intestinal Intraepithelial Neoplasia 73
Enteropathy, Congenital Tufting 57
Congenital Enteropathy 53

Characteristics:

Orphanet epidemiological data:

59
congenital tufting enteropathy
Inheritance: Autosomal recessive; Prevalence: 1-9/100000 (Europe); Age of onset: All ages;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
incidence 1 in 50,000-100,000 in western europe
onset in the neonatal period (0-38 days)


HPO:

32
diarrhea 5, with tufting enteropathy, congenital:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 57 613217
Disease Ontology 12 DOID:0060776
ICD10 33 P78.3
Orphanet 59 ORPHA92050
ICD10 via Orphanet 34 P78.3
MedGen 42 C2750737
MeSH 44 D003968

Summaries for Diarrhea 5, with Tufting Enteropathy, Congenital

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 92050Disease definitionCongenital Tufting Enteropathy is a rare congenital enteropathy presenting with early-onset severe and intractable diarrhea that leads to irreversible intestinal failure.EpidemiologyNo epidemiological data is available, however, the prevalence can be estimated at around 1/200,000 births in Europe. The prevalence is higher in areas with high degrees of consanguinity, but cases have been reported worldwide.Clinical descriptionMost affected patients develop digestive intolerance with vomiting and watery diarrhea within the first few months of life. Diarrhea is severe, chronic and persistent despite bowel rest, resulting in electrolyte imbalance and dehydration. Moreover, an intestinal insufficiency leads to malabsorption, malnutrition, and growth impairment. Although most children present with isolated diarrhea, a small number of congenital tufting enteropathy (CTE) patients present with a syndromic form where diarrhea is associated with non-specific punctuated keratitis, and various malformations such as choanal atresia, esophageal atresia, imperforate anus, dysmorphic features, skeletal dysplasia, and (in one case) Dubowitz syndrome.EtiologyCTE is related to abnormal enterocyte development and differentiation. Mutations in the EPCAM gene (2p21) are seen in 73% of CTE patients and are associated with the isolated intestinal disease. Mutations in the SPINT2 gene (19q13.2) are seen in 21% of CTE cases which are clinically characterized by the syndromic form of the disease. Rarely, CTE patients may present with isolated diarrhea but have no mutations in either EPCAM or SPINT2.Diagnostic methodsDiagnosis is based on the combination of clinical and histological criteria. A congenital chronic diarrhea in the absence of an infectious or an inflammatory process, in association with various degrees of small and large bowel villous atrophy and specific histological abnormalities involving the focal crowding of surface enterocytes resembling ''tufts'', and branching crypts, allow for the diagnosis of CTE. When not all criteria are obvious one can be helped by the association of the non syndromic form of the disease with negative EpCAM immunostaining on patient's duodenal biopsies; or conversely in case of the syndromic form of the disease with a normal EpCAM immunostaining. To date, SPINT2 immunostaining on duodenal biopsies seems useless for the diagnosis. Molecular genetic testing, identifying a mutation in the EPCAM gene or SPINT2 can confirm diagnosis, however, some CTE patients do not have any identified genetic mutations.Differential diagnosisThe differential diagnosis primarily includes other protracted congenital diarrhea disorders such as microvillus inclusion disease, congenital chloride diarrhea, congenital sodium diarrhea, and syndromic diarrhea, as well as glucose-galactose malabsorption (see these terms).Antenatal diagnosisPrenatal diagnosis is available but can only be offered to families where a first case has already been described. The rarity of CTE and the absence of prenatal signs do not make it an appropriate candidate for either antenatal or postnatal mass screening.Genetic counselingCTE is transmitted in an autosomal recessive manner with high prevalence of consanguinity and affected siblings in families.Management and treatmentTo date there is no known curative treatment for CTE. Oral or enteral feedings worsen the diarrhea, however they should be maintained at the minimum tolerated level. CTE patients require daily, long-term parenteral support in order to maintain an adequate nutritional status. Life threatening complications related to intestinal failure and long-term parenteral nutrition may become an indication for intestinal transplantation, thus timing of referral to an expert center is crucial before the onset of severe complications.PrognosisCurrently, children with CTE reach adulthood if long-term parenteral nutrition is conducted appropriately in an experienced center, otherwise the long-term prognosis may be reserved due to the complications of this delicate palliative treatment.Visit the Orphanet disease page for more resources.

MalaCards based summary : Diarrhea 5, with Tufting Enteropathy, Congenital, also known as congenital tufting enteropathy, is related to diarrhea and dementia pugilistica, and has symptoms including infantile diarrhea An important gene associated with Diarrhea 5, with Tufting Enteropathy, Congenital is EPCAM (Epithelial Cell Adhesion Molecule), and among its related pathways/superpathways are Embryonic and Induced Pluripotent Stem Cell Differentiation Pathways and Lineage-specific Markers and CFTR-dependent regulation of ion channels in Airway Epithelium (norm and CF). Affiliated tissues include brain and testes, and related phenotypes are failure to thrive and arthritis

Disease Ontology : 12 A congenital diarrhea characterized by intractable diarrhea of infancy with villous atrophy, absence of inflammation, and intestinal epithelial cell dysplasia manifesting as focal epithelial tufts in the duodenum and jejunum that has material basis in homozygous or compound heterozygous mutation in the EPCAM gene on chromosome 2p21.

OMIM : 57 Congenital tufting enteropathy (CTE) is a rare inherited intractable diarrhea of infancy characterized by villous atrophy and absence of inflammation, with intestinal epithelial cell dysplasia manifesting as focal epithelial tufts in the duodenum and jejunum. CTE presents in the first few months of life with chronic watery diarrhea and failure to thrive, and most affected individuals require parenteral nutrition for normal growth and development (summary by Sivagnanam et al., 2008). Semiquantitative assessment of the epithelial surface in CTE patients revealed that 80 to 90% contained tufts, compared to only 16% in patients with celiac disease and less than 10% in normal jejunum (Reifen et al., 1994). For a discussion of phenotypic and genetic heterogeneity of congenital diarrhea, see DIAR1 (214700). (613217)

CDC : 3 CTE is a brain disease that results from changes in the brain. These changes can affect how a person thinks, feels, acts, and moves. Traumatic brain injuries, including concussions, and repeated hits to the head, called subconcussive head impacts, may lead to CTE.

UniProtKB/Swiss-Prot : 75 Diarrhea 5, with tufting enteropathy, congenital: An intractable diarrhea of infancy characterized by villous atrophy and absence of inflammation, with intestinal epithelial cell dysplasia manifesting as focal epithelial tufts in the duodenum and jejunum.

Related Diseases for Diarrhea 5, with Tufting Enteropathy, Congenital

Diseases related to Diarrhea 5, with Tufting Enteropathy, Congenital via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 15)
# Related Disease Score Top Affiliating Genes
1 diarrhea 27.8 EPCAM MYO5B NEUROG3 SPINT2
2 dementia pugilistica 11.5
3 enterokinase deficiency 10.9
4 diarrhea 2, with microvillus atrophy 10.9
5 insulin-like growth factor i 10.0
6 arthritis 9.9
7 punctate epithelial keratoconjunctivitis 9.9
8 wilms tumor 1 9.9
9 wilms tumor 5 9.9
10 wilms tumor 6 9.9
11 crohn's disease 9.9
12 encephalopathy 9.9
13 secretory diarrhea 9.7 MYO5B SPINT2
14 chromophobe renal cell carcinoma 9.5 EPCAM PRSS8
15 congenital diarrhea 8.4 EPCAM MYO5B NEUROG3 SPINT2

Graphical network of the top 20 diseases related to Diarrhea 5, with Tufting Enteropathy, Congenital:



Diseases related to Diarrhea 5, with Tufting Enteropathy, Congenital

Symptoms & Phenotypes for Diarrhea 5, with Tufting Enteropathy, Congenital

Symptoms via clinical synopsis from OMIM:

57
Growth Weight:
low birth weight (some)

Abdomen Gastrointestinal:
diarrhea, intractable
villous atrophy
crowded epithelial cells forming tufts
no lamina propria mononuclear cell infiltration
dependent on total parenteral nutrition (tpn)

Laboratory Abnormalities:
electrolyte disturbances from intractable diarrhea

Growth Other:
failure to thrive

Skeletal Limbs:
arthritis, chronic inflammatory (in some patients)


Clinical features from OMIM:

613217

Human phenotypes related to Diarrhea 5, with Tufting Enteropathy, Congenital:

32
# Description HPO Frequency HPO Source Accession
1 failure to thrive 32 HP:0001508
2 arthritis 32 occasional (7.5%) HP:0001369
3 small for gestational age 32 occasional (7.5%) HP:0001518
4 villous atrophy 32 HP:0011473
5 intractable diarrhea 32 HP:0002041

UMLS symptoms related to Diarrhea 5, with Tufting Enteropathy, Congenital:


infantile diarrhea

MGI Mouse Phenotypes related to Diarrhea 5, with Tufting Enteropathy, Congenital:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 digestive/alimentary MP:0005381 9.26 EPCAM MYO5B NEUROG3 TREH
2 homeostasis/metabolism MP:0005376 9.02 EPCAM MYO5B NEUROG3 PRSS8 TREH

Drugs & Therapeutics for Diarrhea 5, with Tufting Enteropathy, Congenital

Search Clinical Trials , NIH Clinical Center for Diarrhea 5, with Tufting Enteropathy, Congenital

Genetic Tests for Diarrhea 5, with Tufting Enteropathy, Congenital

Genetic tests related to Diarrhea 5, with Tufting Enteropathy, Congenital:

# Genetic test Affiliating Genes
1 Diarrhea 5, with Tufting Enteropathy, Congenital 29 EPCAM

Anatomical Context for Diarrhea 5, with Tufting Enteropathy, Congenital

MalaCards organs/tissues related to Diarrhea 5, with Tufting Enteropathy, Congenital:

41
Brain, Testes

Publications for Diarrhea 5, with Tufting Enteropathy, Congenital

Articles related to Diarrhea 5, with Tufting Enteropathy, Congenital:

(show all 11)
# Title Authors Year
1
Congenital tufting enteropathy and chronic arthritis: a clinical and radiological perspective. ( 27558188 )
2016
2
Genetic analysis of Italian patients with congenital tufting enteropathy. ( 26684320 )
2016
3
A Novel Nonsense Mutation in the EpCAM Gene in a Patient With Congenital Tufting Enteropathy. ( 24048167 )
2014
4
Genetic characterization of congenital tufting enteropathy: epcam associated phenotype and involvement of SPINT2 in the syndromic form. ( 24142340 )
2013
5
Absence of cell-surface EpCAM in congenital tufting enteropathy. ( 23462293 )
2013
6
mTrop1/Epcam knockout mice develop congenital tufting enteropathy through dysregulation of intestinal E-cadherin/I^-catenin. ( 23209569 )
2012
7
Congenital tufting enteropathy in the era of molecular genetics. ( 21691225 )
2011
8
A founder effect at the EPCAM locus in Congenital Tufting Enteropathy in the Arabic Gulf. ( 21315192 )
2011
9
Further evidence for EpCAM as the gene for congenital tufting enteropathy. ( 20034091 )
2010
10
Superficial punctate keratitis and conjunctival erosions associated with congenital tufting enteropathy. ( 20447614 )
2010
11
Identification of EpCAM as the gene for congenital tufting enteropathy. ( 18572020 )
2008

Variations for Diarrhea 5, with Tufting Enteropathy, Congenital

UniProtKB/Swiss-Prot genetic disease variations for Diarrhea 5, with Tufting Enteropathy, Congenital:

75
# Symbol AA change Variation ID SNP ID
1 EPCAM p.Cys66Tyr VAR_063829 rs267606785

ClinVar genetic disease variations for Diarrhea 5, with Tufting Enteropathy, Congenital:

6
(show all 14)
# Gene Variation Type Significance SNP ID Assembly Location
1 EPCAM NM_002354.2(EPCAM): c.491+1G> A single nucleotide variant Pathogenic rs606231203 GRCh38 Chromosome 2, 47375300: 47375300
2 EPCAM NM_002354.2(EPCAM): c.491+1G> A single nucleotide variant Pathogenic rs606231203 GRCh37 Chromosome 2, 47602439: 47602439
3 EPCAM NM_002354.2(EPCAM): c.197G> A (p.Cys66Tyr) single nucleotide variant Pathogenic rs267606785 GRCh37 Chromosome 2, 47600959: 47600959
4 EPCAM NM_002354.2(EPCAM): c.197G> A (p.Cys66Tyr) single nucleotide variant Pathogenic rs267606785 GRCh38 Chromosome 2, 47373820: 47373820
5 EPCAM NM_002354.2(EPCAM): c.499dupC (p.Gln167Profs) duplication Pathogenic rs606231204 GRCh38 Chromosome 2, 47377021: 47377021
6 EPCAM NM_002354.2(EPCAM): c.499dupC (p.Gln167Profs) duplication Pathogenic rs606231204 GRCh37 Chromosome 2, 47604160: 47604160
7 EPCAM NM_002354.2(EPCAM): c.412C> T (p.Arg138Ter) single nucleotide variant Pathogenic rs397514661 GRCh37 Chromosome 2, 47601174: 47601174
8 EPCAM NM_002354.2(EPCAM): c.412C> T (p.Arg138Ter) single nucleotide variant Pathogenic rs397514661 GRCh38 Chromosome 2, 47374035: 47374035
9 EPCAM NM_002354.2(EPCAM): c.556-14A> G single nucleotide variant Pathogenic rs376155665 GRCh38 Chromosome 2, 47378939: 47378939
10 EPCAM NM_002354.2(EPCAM): c.556-14A> G single nucleotide variant Pathogenic rs376155665 GRCh37 Chromosome 2, 47606078: 47606078
11 EPCAM NM_002354.2(EPCAM): c.492-2A> G single nucleotide variant Pathogenic rs606231281 GRCh38 Chromosome 2, 47377012: 47377012
12 EPCAM NM_002354.2(EPCAM): c.492-2A> G single nucleotide variant Pathogenic rs606231281 GRCh37 Chromosome 2, 47604151: 47604151
13 EPCAM NM_002354.2(EPCAM): c.373_374insC (p.Arg125Thrfs) insertion Pathogenic GRCh37 Chromosome 2, 47601135: 47601136
14 EPCAM NM_002354.2(EPCAM): c.373_374insC (p.Arg125Thrfs) insertion Pathogenic GRCh38 Chromosome 2, 47373996: 47373997

Expression for Diarrhea 5, with Tufting Enteropathy, Congenital

Search GEO for disease gene expression data for Diarrhea 5, with Tufting Enteropathy, Congenital.

Pathways for Diarrhea 5, with Tufting Enteropathy, Congenital

Pathways related to Diarrhea 5, with Tufting Enteropathy, Congenital according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.08 EPCAM NEUROG3
2 10.17 PRSS8 SPINT2

GO Terms for Diarrhea 5, with Tufting Enteropathy, Congenital

Cellular components related to Diarrhea 5, with Tufting Enteropathy, Congenital according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 anchored component of plasma membrane GO:0046658 8.62 PRSS8 TREH

Sources for Diarrhea 5, with Tufting Enteropathy, Congenital

3 CDC
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62 PubMed
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69 SNOMED-CT via HPO
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74 UMLS via Orphanet
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