DIAR3
MCID: DRR017
MIFTS: 35

Diarrhea 3, Secretory Sodium, Congenital, with or Without Other Congenital Anomalies (DIAR3)

Categories: Gastrointestinal diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Diarrhea 3, Secretory Sodium, Congenital, with or Without Other...

MalaCards integrated aliases for Diarrhea 3, Secretory Sodium, Congenital, with or Without Other Congenital Anomalies:

Name: Diarrhea 3, Secretory Sodium, Congenital, with or Without Other Congenital Anomalies 57 72 6
Diarrhea 3, Secretory Sodium, Congenital, Syndromic 57 72 29 13 6
Congenital Sodium Diarrhea 58 72
Diar3 57 72
Csd 57 72
Congenital Secretory Sodium Diarrhoea 3 with or Without Other Congenital Anomalies 12
Congenital Secretory Sodium Diarrhea 3 with or Without Other Congenital Anomalies 12
Diarrhea, Type 3, Secretory Sodium, Congenital, Syndromic 39
Congenital Secretory Sodium Diarrhoea 3 Syndromic 12
Congenital Secretory Sodium Diarrhea 3 Syndromic 12
Congenital Secretory Diarrhea, Sodium Type 70
Non-Syndromic Congenital Sodium Diarrhea 58
Congenital Secretory Sodium Diarrhoea 3 12
Congenital Secretory Sodium Diarrhea 3 12
Sodium Diarrhea, Congenital; Csd 57
Sodium Diarrhea, Congenital 57
Na-H Exchange Deficiency 58

Characteristics:

Orphanet epidemiological data:

58
congenital sodium diarrhea
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide);

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive


HPO:

31
diarrhea 3, secretory sodium, congenital, with or without other congenital anomalies:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare gastroenterological diseases


External Ids:

Disease Ontology 12 DOID:0060781
OMIM® 57 270420
OMIM Phenotypic Series 57 PS214700
MeSH 44 D003968
ICD10 32 P78.3
ICD10 via Orphanet 33 P78.3
UMLS via Orphanet 71 C0267663
Orphanet 58 ORPHA103908
UMLS 70 C0267663

Summaries for Diarrhea 3, Secretory Sodium, Congenital, with or Without Other...

UniProtKB/Swiss-Prot : 72 Diarrhea 3, secretory sodium, congenital, with or without other congenital anomalies: A disease characterized by life-threatening secretory diarrhea, severe metabolic acidosis and hyponatremia. Hyponatremia is secondary to extraordinarily high fecal sodium loss, with low or normal excretion of urinary sodium, in the absence of infectious, autoimmune and endocrine causes.

MalaCards based summary : Diarrhea 3, Secretory Sodium, Congenital, with or Without Other Congenital Anomalies, also known as diarrhea 3, secretory sodium, congenital, syndromic, is related to diarrhea 5, with tufting enteropathy, congenital and diarrhea 8, secretory sodium, congenital, and has symptoms including diarrhea and watery diarrhea. An important gene associated with Diarrhea 3, Secretory Sodium, Congenital, with or Without Other Congenital Anomalies is SPINT2 (Serine Peptidase Inhibitor, Kunitz Type 2). Affiliated tissues include bone and olfactory bulb, and related phenotypes are macrocephaly and low-set ears

Disease Ontology : 12 A secretory diarrhea that has material basis in homozygous or compound heterozygous mutation in the SPINT2 gene on chromosome 19q13.

More information from OMIM: 270420 PS214700

Related Diseases for Diarrhea 3, Secretory Sodium, Congenital, with or Without Other...

Diseases related to Diarrhea 3, Secretory Sodium, Congenital, with or Without Other Congenital Anomalies via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 50)
# Related Disease Score Top Affiliating Genes
1 diarrhea 5, with tufting enteropathy, congenital 31.4 SPINT2 SLC9A3
2 diarrhea 8, secretory sodium, congenital 31.1 SLC9A3-AS1 SLC9A3
3 secretory diarrhea 29.7 SPINT2 SLC9A3 GUCY2C
4 diarrhea 29.5 SPINT2 SLC9A3-AS1 SLC9A3 GUCY2C
5 cat-scratch disease 11.5
6 syndromic congenital sodium diarrhea 11.3
7 neuroretinitis 11.0
8 migraine with or without aura 1 10.4
9 metabolic acidosis 10.3
10 polyhydramnios 10.2
11 choanal atresia, posterior 10.1
12 congenital chloride diarrhea 10.1
13 autosomal recessive disease 10.1
14 migraine with aura 10.0
15 bartonellosis 10.0
16 lymphadenitis 10.0
17 headache 10.0
18 coloboma of macula 9.9
19 hypertelorism 9.9
20 keratitis, hereditary 9.9
21 anus, imperforate 9.9
22 inflammatory bowel disease 9.9
23 alternating exotropia 9.9
24 exotropia 9.9
25 acute kidney failure 9.9
26 bartter disease 9.9
27 kidney disease 9.9
28 intestinal obstruction 9.9
29 cleft lip 9.9
30 cleft lip/palate 9.9
31 papillomatosis, confluent and reticulated 9.9
32 ifap syndrome 2 9.9
33 familial episodic pain syndrome 9.9
34 amnestic disorder 9.9
35 migraine without aura 9.9
36 conduct disorder 9.9
37 uveitis 9.9
38 optic nerve disease 9.9
39 skin disease 9.9
40 systemic scleroderma 9.9
41 cervical adenitis 9.9
42 conjunctivitis 9.9
43 lung disease 9.9
44 neuropathy 9.9
45 scotoma 9.9
46 lymph node disease 9.9
47 argyria 9.9
48 congenital diarrhea 9.7 SPINT2 SLC9A3
49 meconium ileus 9.7 SLC9A3 GUCY2C
50 ileus 9.6 SLC9A3 GUCY2C

Graphical network of the top 20 diseases related to Diarrhea 3, Secretory Sodium, Congenital, with or Without Other Congenital Anomalies:



Diseases related to Diarrhea 3, Secretory Sodium, Congenital, with or Without Other Congenital Anomalies

Symptoms & Phenotypes for Diarrhea 3, Secretory Sodium, Congenital, with or Without Other...

Human phenotypes related to Diarrhea 3, Secretory Sodium, Congenital, with or Without Other Congenital Anomalies:

31 (show all 15)
# Description HPO Frequency HPO Source Accession
1 macrocephaly 31 occasional (7.5%) HP:0000256
2 low-set ears 31 occasional (7.5%) HP:0000369
3 anal atresia 31 occasional (7.5%) HP:0002023
4 intestinal malrotation 31 occasional (7.5%) HP:0002566
5 rectovaginal fistula 31 occasional (7.5%) HP:0000143
6 ureteral duplication 31 occasional (7.5%) HP:0000073
7 optic nerve coloboma 31 occasional (7.5%) HP:0000588
8 cutis laxa 31 occasional (7.5%) HP:0000973
9 hypertelorism 31 HP:0000316
10 choanal atresia 31 HP:0000453
11 polyhydramnios 31 HP:0001561
12 abnormality of metabolism/homeostasis 31 HP:0001939
13 corneal erosion 31 HP:0200020
14 abdominal distention 31 HP:0003270
15 secretory diarrhea 31 HP:0005208

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Eyes:
hypertelorism
corneal erosions
lacrimal duct imperforation (rare)
coloboma of optic nerve (rare)

Prenatal Manifestations Amniotic Fluid:
polyhydramnios

Head And Neck Face:
fistula of philtrum (rare)

Abdomen External Features:
abdominal distention at birth

Genitourinary Ureters:
ureteral duplication (rare)

Skeletal Hands:
hexadactyly (rare)

Skin Nails Hair Hair:
pilar dysplasia (in some patients)

Head And Neck Nose:
choanal atresia
olfactory bulb agenesis (rare)

Head And Neck Head:
macrocephaly (rare)

Head And Neck Ears:
deafness due to bilateral cochlear malformation (rare)
low-set ears (rare)

Abdomen Gastrointestinal:
congenital secretory sodium diarrhea
enterocyte tufting (in some patients)
imperforate anus (rare)
rectovaginal fistula (rare)
multiple intestinal atresia (rare)
more
Skeletal:
bone anomalies (rare)

Skin Nails Hair Skin:
cutaneous laxity (rare)

Clinical features from OMIM®:

270420 (Updated 05-Apr-2021)

UMLS symptoms related to Diarrhea 3, Secretory Sodium, Congenital, with or Without Other Congenital Anomalies:


diarrhea; watery diarrhea

MGI Mouse Phenotypes related to Diarrhea 3, Secretory Sodium, Congenital, with or Without Other Congenital Anomalies:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 digestive/alimentary MP:0005381 8.8 GUCY2C SLC9A3 SPINT2

Drugs & Therapeutics for Diarrhea 3, Secretory Sodium, Congenital, with or Without Other...

Search Clinical Trials , NIH Clinical Center for Diarrhea 3, Secretory Sodium, Congenital, with or Without Other Congenital Anomalies

Genetic Tests for Diarrhea 3, Secretory Sodium, Congenital, with or Without Other...

Genetic tests related to Diarrhea 3, Secretory Sodium, Congenital, with or Without Other Congenital Anomalies:

# Genetic test Affiliating Genes
1 Diarrhea 3, Secretory Sodium, Congenital, Syndromic 29

Anatomical Context for Diarrhea 3, Secretory Sodium, Congenital, with or Without Other...

MalaCards organs/tissues related to Diarrhea 3, Secretory Sodium, Congenital, with or Without Other Congenital Anomalies:

40
Bone, Olfactory Bulb

Publications for Diarrhea 3, Secretory Sodium, Congenital, with or Without Other...

Articles related to Diarrhea 3, Secretory Sodium, Congenital, with or Without Other Congenital Anomalies:

(show all 15)
# Title Authors PMID Year
1
SPINT2 (HAI-2) missense variants identified in congenital sodium diarrhea/tufting enteropathy affect the ability of HAI-2 to inhibit prostasin but not matriptase. 57 6
30445423 2019
2
Genetic characterization of congenital tufting enteropathy: epcam associated phenotype and involvement of SPINT2 in the syndromic form. 6 57
24142340 2014
3
Syndromic congenital diarrhea because of the SPINT2 mutation showing enterocyte tufting and unique electron microscopy findings. 6 57
23689399 2013
4
Case of syndromic tufting enteropathy harbors SPINT2 mutation seen in congenital sodium diarrhea. 57 6
20009592 2010
5
Mutations in SPINT2 cause a syndromic form of congenital sodium diarrhea. 6 57
19185281 2009
6
A new syndrome of tufting enteropathy and choanal atresia, with ophthalmologic, hematologic and hair abnormalities. 6 57
17786112 2007
7
Congenital sodium diarrhea is an autosomal recessive disorder of sodium/proton exchange but unrelated to known candidate genes. 57 6
11113072 2000
8
Congenital Na+ diarrhea: a new type of secretory diarrhea. 6 57
3880821 1985
9
Congenital Sodium Diarrhea by mutation of the SLC9A3 gene. 6
31276831 2019
10
Application of Whole Exome Sequencing in Congenital Secretory Diarrhea Diagnosis. 6
30633106 2019
11
Reduced sodium/proton exchanger NHE3 activity causes congenital sodium diarrhea. 6
26358773 2015
12
Congenital sodium diarrhea with a partial defect in jejunal brush border membrane sodium transport, normal rectal transport, and resolving diarrhea. 57
1403458 1992
13
Defective jejunal brush border membrane sodium/proton exchange in association with lethal familial protracted diarrhoea. 57
1964660 1990
14
Defective jejunal brush-border Na+/H+ exchange: a cause of congenital secretory diarrhoea. 57
2860286 1985
15
Genetic analysis of calf health in Charolais beef cattle. 61
29471383 2018

Variations for Diarrhea 3, Secretory Sodium, Congenital, with or Without Other...

ClinVar genetic disease variations for Diarrhea 3, Secretory Sodium, Congenital, with or Without Other Congenital Anomalies:

6 (show all 19)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 SPINT2 NM_021102.4(SPINT2):c.593-1G>A SNV Pathogenic 5204 rs606231154 GRCh37: 19:38782479-38782479
GRCh38: 19:38291839-38291839
2 SPINT2 NM_021102.4(SPINT2):c.337+2T>C SNV Pathogenic 5206 rs606231155 GRCh37: 19:38778577-38778577
GRCh38: 19:38287937-38287937
3 SPINT2 NM_021102.4(SPINT2):c.553+2T>A SNV Pathogenic 5207 rs112576957 GRCh37: 19:38780922-38780922
GRCh38: 19:38290282-38290282
4 SPINT2 NM_021102.4(SPINT2):c.1A>T (p.Met1Leu) SNV Pathogenic 5208 rs121908404 GRCh37: 19:38755533-38755533
GRCh38: 19:38264893-38264893
5 SLC9A3 NM_004174.4(SLC9A3):c.341_343TCT[3] (p.Phe117del) Microsatellite Pathogenic 224596 rs776026092 GRCh37: 5:492046-492048
GRCh38: 5:491931-491933
6 SLC9A3 NM_004174.4(SLC9A3):c.1145G>A (p.Arg382Gln) SNV Pathogenic 224597 rs766076524 GRCh37: 5:483385-483385
GRCh38: 5:483270-483270
7 SLC9A3 NM_004174.4(SLC9A3):c.932C>T (p.Ala311Val) SNV Pathogenic 224595 rs869312806 GRCh37: 5:484635-484635
GRCh38: 5:484520-484520
8 SLC9A3-AS1 , SLC9A3 NM_004174.4(SLC9A3):c.1745del (p.Ser582fs) Deletion Pathogenic 224598 rs869320692 GRCh37: 5:477462-477462
GRCh38: 5:477347-477347
9 SPINT2 NM_021102.4(SPINT2):c.447G>A (p.Trp149Ter) SNV Pathogenic 635284 rs780880496 GRCh37: 19:38780814-38780814
GRCh38: 19:38290174-38290174
10 SLC9A3 NM_004174.4(SLC9A3):c.782dup (p.Thr262fs) Duplication Pathogenic 224600 rs869320759 GRCh37: 5:484784-484785
GRCh38: 5:484669-484670
11 SLC9A3 D405G Variation Pathogenic 986310 GRCh37:
GRCh38:
12 SPINT2 NM_021102.4(SPINT2):c.488A>G (p.Tyr163Cys) SNV Pathogenic 5205 rs121908403 GRCh37: 19:38780855-38780855
GRCh38: 19:38290215-38290215
13 SLC9A3 NM_004174.4(SLC9A3):c.805G>A (p.Ala269Thr) SNV Pathogenic 224599 rs869312807 GRCh37: 5:484762-484762
GRCh38: 5:484647-484647
14 SPINT2 NM_021102.4(SPINT2):c.502G>A (p.Gly168Ser) SNV Pathogenic 157607 rs606231284 GRCh37: 19:38780869-38780869
GRCh38: 19:38290229-38290229
15 SLC9A3 NM_004174.4(SLC9A3):c.1039G>A (p.Glu347Lys) SNV Likely pathogenic 625848 rs766583286 GRCh37: 5:483491-483491
GRCh38: 5:483376-483376
16 SLC9A3 NM_004174.4(SLC9A3):c.932+1G>A SNV Likely pathogenic 592108 rs144524702 GRCh37: 5:484634-484634
GRCh38: 5:484519-484519
17 SPINT2 NM_021102.4(SPINT2):c.553C>T (p.Arg185Cys) SNV Uncertain significance 1028719 GRCh37: 19:38780920-38780920
GRCh38: 19:38290280-38290280
18 SLC9A3-AS1 , SLC9A3 NM_004174.4(SLC9A3):c.1862A>G (p.Gln621Arg) SNV Uncertain significance 1034058 GRCh37: 5:476686-476686
GRCh38: 5:476571-476571
19 SLC9A3-AS1 , SLC9A3 NM_004174.4(SLC9A3):c.1814G>A (p.Arg605Gln) SNV Uncertain significance 547876 rs146547322 GRCh37: 5:476734-476734
GRCh38: 5:476619-476619

UniProtKB/Swiss-Prot genetic disease variations for Diarrhea 3, Secretory Sodium, Congenital, with or Without Other Congenital Anomalies:

72
# Symbol AA change Variation ID SNP ID
1 SPINT2 p.Tyr163Cys VAR_058718 rs121908403

Expression for Diarrhea 3, Secretory Sodium, Congenital, with or Without Other...

Search GEO for disease gene expression data for Diarrhea 3, Secretory Sodium, Congenital, with or Without Other Congenital Anomalies.

Pathways for Diarrhea 3, Secretory Sodium, Congenital, with or Without Other...

GO Terms for Diarrhea 3, Secretory Sodium, Congenital, with or Without Other...

Sources for Diarrhea 3, Secretory Sodium, Congenital, with or Without Other...

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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