DIAR5
MCID: DRR003
MIFTS: 50

Diarrhea 5, with Tufting Enteropathy, Congenital (DIAR5)

Categories: Gastrointestinal diseases, Genetic diseases, Metabolic diseases, Rare 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 58 76 30 13 6 74
Congenital Tufting Enteropathy 12 60 76
Diar5 58 12 76
Cte 58 76 3
Congenital Diarrhea 5 with Tufting Enteropathy 12 15
Intestinal Epithelial Cell Dysplasia 58 76
Intestinal Epithelial Dysplasia 54 60
Tufting Enteropathy 12 54
Ied 54 60
Congenital Familial Intractable Diarrhea with Epithelial or Epithelium Abnormalities 12
Congenital Familial Intractable Diarrhea with Enterocytes Assembly Abnormalities 54
Diarrhea, Type 5, with Tufting Enteropathy, Congenital 41
Enteropathy, Congenital Tufting; Cte 58
Intestinal Intraepithelial Neoplasia 74
Enteropathy, Congenital Tufting 58
Congenital Enteropathy 54

Characteristics:

Orphanet epidemiological data:

60
congenital tufting enteropathy
Inheritance: Autosomal recessive; Prevalence: 1-9/100000 (Europe); Age of onset: All ages;

OMIM:

58
Inheritance:
autosomal recessive

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


HPO:

33
diarrhea 5, with tufting enteropathy, congenital:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0060776
OMIM 58 613217
MeSH 45 D003968
ICD10 34 P78.3
ICD10 via Orphanet 35 P78.3
Orphanet 60 ORPHA92050
MedGen 43 C2750737

Summaries for Diarrhea 5, with Tufting Enteropathy, Congenital

NIH Rare Diseases : 54 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.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 chromophobe renal cell carcinoma and diarrhea, 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 MET promotes cell motility and Adhesion. Affiliated tissues include heart, brain and t cells, and related phenotypes are arthritis and small for gestational age

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 : 58 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 genetic heterogeneity of diarrhea, see DIAR1 (214700). (613217)

CDC : 3 CTE is a brain disease that can only be diagnosed after death. It has been linked to specific changes in the brain that affect how the brain works. The research to-date suggests that CTE is caused in part by repeated traumatic brain injuries, including concussions, and repeated hits to the head, called subconcussive head impacts.

UniProtKB/Swiss-Prot : 76 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.

Wikipedia : 77 Congenital tufting enteropathy is an inherited disorder of the small intestine that presents with... more...

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 top 50) (show all 3881)
# Related Disease Score Top Affiliating Genes
1 chromophobe renal cell carcinoma 31.5 EPCAM PRSS8
2 diarrhea 30.5 EPCAM SPINT2
3 congenital diarrhea 29.8 EPCAM SPINT2
4 bare lymphocyte syndrome, type i 12.5
5 mitochondrial complex i deficiency, nuclear type 1 12.5
6 carnitine palmitoyltransferase i deficiency 12.4
7 carbamoyl phosphate synthetase i deficiency, hyperammonemia due to 12.4
8 spinal muscular atrophy, type i 12.4
9 cataract 13 with adult i phenotype 12.4
10 dentin dysplasia, type i 12.4
11 complement factor i deficiency 12.4
12 trichorhinophalangeal syndrome, type i 12.4
13 blood group, i system 12.4
14 glutaric acidemia i 12.4
15 tyrosinemia, type i 12.3
16 3-methylglutaconic aciduria, type i 12.3
17 osteogenesis imperfecta, type i 12.3
18 orofaciodigital syndrome i 12.3
19 corneal dystrophy, lattice type i 12.3
20 scheie syndrome 12.3
21 microcephalic osteodysplastic primordial dwarfism, type i 12.3
22 atelosteogenesis, type i 12.3
23 corticosterone methyloxidase type i deficiency 12.3
24 pseudohypoaldosteronism, type i, autosomal recessive 12.3
25 chiari malformation type i 12.3
26 pseudohypoaldosteronism, type i, autosomal dominant 12.3
27 gaucher disease, type i 12.3
28 thanatophoric dysplasia, type i 12.3
29 usher syndrome, type i 12.3
30 hyperoxaluria, primary, type i 12.3
31 xanthinuria, type i 12.3
32 schindler disease, type i 12.3
33 bipolar i disorder 12.3
34 fanconi anemia, complementation group i 12.3
35 multiple endocrine neoplasia, type i 12.2
36 plasminogen deficiency, type i 12.2
37 mitochondrial complex i deficiency, nuclear type 20 12.2
38 lynch syndrome i 12.2
39 porphyria cutanea tarda, type i 12.2
40 angioedema, hereditary, type i 12.2
41 autoimmune polyendocrine syndrome, type i, with or without reversible metaphyseal dysplasia 12.2
42 mitochondrial complex i deficiency, nuclear type 10 12.2
43 mitochondrial complex i deficiency, nuclear type 16 12.2
44 mitochondrial complex i deficiency, nuclear type 2 12.2
45 mitochondrial complex i deficiency, nuclear type 4 12.2
46 mitochondrial complex i deficiency, nuclear type 7 12.2
47 mitochondrial complex i deficiency, nuclear type 29 12.2
48 mitochondrial complex i deficiency, nuclear type 8 12.2
49 mitochondrial complex i deficiency, nuclear type 11 12.2
50 mitochondrial complex i deficiency, nuclear type 17 12.2

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

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

33
# Description HPO Frequency HPO Source Accession
1 arthritis 33 occasional (7.5%) HP:0001369
2 small for gestational age 33 occasional (7.5%) HP:0001518
3 failure to thrive 33 HP:0001508
4 villous atrophy 33 HP:0011473
5 intractable diarrhea 33 HP:0002041

Symptoms via clinical synopsis from OMIM:

58
Growth Other:
failure to thrive

Growth Weight:
low birth weight (some)

Laboratory Abnormalities:
electrolyte disturbances from intractable diarrhea

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

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

Clinical features from OMIM:

613217

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


infantile diarrhea

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

27
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Negative genetic interaction between BLM-/- and BLM+/+ GR00255-A-1 8.8 HGFAC PRSS8 SPINT2

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

47
# Description MGI Source Accession Score Top Affiliating Genes
1 embryo MP:0005380 9.46 EPCAM PRSS8 SPINT2 ST14
2 limbs/digits/tail MP:0005371 9.13 PRSS8 SPINT2 ST14
3 mortality/aging MP:0010768 9.02 EPCAM HGFAC PRSS8 SPINT2 ST14

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

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Characterization Phenotypic and Genetic Study of the Intestinal Epithelial Dysplasia or Tufting Enteropathy (TE) Completed NCT01114035 Not Applicable

Search 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 30 EPCAM

Anatomical Context for Diarrhea 5, with Tufting Enteropathy, Congenital

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

42
Heart, Brain, T Cells, Bone, Kidney, Breast, Lung

Publications for Diarrhea 5, with Tufting Enteropathy, Congenital

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

(show all 16)
# Title Authors Year
1
EPCAM mutation update: Variants associated with congenital tufting enteropathy and Lynch syndrome. ( 30461124 )
2018
2
Novel Mutations in EPCAM Cause Congenital Tufting Enteropathy. ( 27875355 )
2018
3
Loss of HAI-2 in mice with decreased prostasin activity leads to an early-onset intestinal failure resembling congenital tufting enteropathy. ( 29617460 )
2018
4
Kocuria kristinae-caused sepsis in an infant with congenital tufting enteropathy. ( 29168373 )
2017
5
Congenital tufting enteropathy and chronic arthritis: a clinical and radiological perspective. ( 27558188 )
2016
6
Genetic analysis of Italian patients with congenital tufting enteropathy. ( 26684320 )
2016
7
A novel nonsense mutation in the EpCAM gene in a patient with congenital tufting enteropathy. ( 24048167 )
2014
8
Genetic characterization of congenital tufting enteropathy: epcam associated phenotype and involvement of SPINT2 in the syndromic form. ( 24142340 )
2014
9
Absence of cell-surface EpCAM in congenital tufting enteropathy. ( 23462293 )
2013
10
mTrop1/Epcam knockout mice develop congenital tufting enteropathy through dysregulation of intestinal E-cadherin/β-catenin. ( 23209569 )
2012
11
Congenital tufting enteropathy in the era of molecular genetics. ( 21691225 )
2011
12
A founder effect at the EPCAM locus in Congenital Tufting Enteropathy in the Arabic Gulf. ( 21315192 )
2011
13
Superficial punctate keratitis and conjunctival erosions associated with congenital tufting enteropathy. ( 20447614 )
2010
14
Further evidence for EpCAM as the gene for congenital tufting enteropathy. ( 20034091 )
2010
15
Tufting enteropathy and chronic arthritis: a newly recognized association with a novel EpCAM gene mutation. ( 19820410 )
2009
16
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:

76
# 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 24)
# 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.426-1G> A single nucleotide variant Uncertain significance rs373597944 GRCh38 Chromosome 2, 47375233: 47375233
4 EPCAM NM_002354.2(EPCAM): c.426-1G> A single nucleotide variant Uncertain significance rs373597944 GRCh37 Chromosome 2, 47602372: 47602372
5 EPCAM NM_002354.2(EPCAM): c.197G> A (p.Cys66Tyr) single nucleotide variant Pathogenic rs267606785 GRCh37 Chromosome 2, 47600959: 47600959
6 EPCAM NM_002354.2(EPCAM): c.197G> A (p.Cys66Tyr) single nucleotide variant Pathogenic rs267606785 GRCh38 Chromosome 2, 47373820: 47373820
7 EPCAM NM_002354.2(EPCAM): c.499dupC (p.Gln167Profs) duplication Pathogenic rs606231204 GRCh38 Chromosome 2, 47377021: 47377021
8 EPCAM NM_002354.2(EPCAM): c.499dupC (p.Gln167Profs) duplication Pathogenic rs606231204 GRCh37 Chromosome 2, 47604160: 47604160
9 EPCAM NM_002354.2(EPCAM): c.412C> T (p.Arg138Ter) single nucleotide variant Pathogenic rs397514661 GRCh37 Chromosome 2, 47601174: 47601174
10 EPCAM NM_002354.2(EPCAM): c.412C> T (p.Arg138Ter) single nucleotide variant Pathogenic rs397514661 GRCh38 Chromosome 2, 47374035: 47374035
11 EPCAM NM_002354.2(EPCAM): c.577A> G (p.Ile193Val) single nucleotide variant Uncertain significance rs200676965 GRCh37 Chromosome 2, 47606113: 47606113
12 EPCAM NM_002354.2(EPCAM): c.577A> G (p.Ile193Val) single nucleotide variant Uncertain significance rs200676965 GRCh38 Chromosome 2, 47378974: 47378974
13 EPCAM NM_002354.2(EPCAM): c.556-14A> G single nucleotide variant Pathogenic rs376155665 GRCh38 Chromosome 2, 47378939: 47378939
14 EPCAM NM_002354.2(EPCAM): c.556-14A> G single nucleotide variant Pathogenic rs376155665 GRCh37 Chromosome 2, 47606078: 47606078
15 EPCAM NM_002354.2(EPCAM): c.492-2A> G single nucleotide variant Pathogenic rs606231281 GRCh38 Chromosome 2, 47377012: 47377012
16 EPCAM NM_002354.2(EPCAM): c.492-2A> G single nucleotide variant Pathogenic rs606231281 GRCh37 Chromosome 2, 47604151: 47604151
17 EPCAM NM_002354.2(EPCAM): c.491+1G> T single nucleotide variant Pathogenic rs606231203 GRCh37 Chromosome 2, 47602439: 47602439
18 EPCAM NM_002354.2(EPCAM): c.491+1G> T single nucleotide variant Pathogenic rs606231203 GRCh38 Chromosome 2, 47375300: 47375300
19 EPCAM NM_002354.2(EPCAM): c.179C> T (p.Ser60Leu) single nucleotide variant Uncertain significance rs147494515 GRCh37 Chromosome 2, 47600704: 47600704
20 EPCAM NM_002354.2(EPCAM): c.179C> T (p.Ser60Leu) single nucleotide variant Uncertain significance rs147494515 GRCh38 Chromosome 2, 47373565: 47373565
21 EPCAM NM_002354.2(EPCAM): c.429G> A (p.Trp143Ter) single nucleotide variant Pathogenic rs878854488 GRCh38 Chromosome 2, 47375237: 47375237
22 EPCAM NM_002354.2(EPCAM): c.429G> A (p.Trp143Ter) single nucleotide variant Pathogenic rs878854488 GRCh37 Chromosome 2, 47602376: 47602376
23 EPCAM NM_002354.2(EPCAM): c.373_374insC (p.Arg125Thrfs) insertion Pathogenic rs1553342984 GRCh37 Chromosome 2, 47601135: 47601136
24 EPCAM NM_002354.2(EPCAM): c.373_374insC (p.Arg125Thrfs) insertion Pathogenic rs1553342984 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

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 extracellular region GO:0005576 9.26 HGFAC PRSS8 SPINT2 ST14
2 basolateral plasma membrane GO:0016323 9.16 EPCAM ST14
3 extrinsic component of plasma membrane GO:0019897 8.62 PRSS8 ST14

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

# Name GO ID Score Top Affiliating Genes
1 proteolysis GO:0006508 9.43 HGFAC PRSS8 ST14
2 cornification GO:0070268 9.16 PRSS8 ST14
3 neural tube closure GO:0001843 8.96 SPINT2 ST14
4 epithelial cell morphogenesis involved in placental branching GO:0060672 8.62 SPINT2 ST14

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

# Name GO ID Score Top Affiliating Genes
1 peptidase activity GO:0008233 9.33 HGFAC PRSS8 ST14
2 serine-type endopeptidase activity GO:0004252 9.13 HGFAC PRSS8 ST14
3 serine-type peptidase activity GO:0008236 8.8 HGFAC PRSS8 ST14

Sources for Diarrhea 5, with Tufting Enteropathy, Congenital

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
Content
Loading form....