MCID: CHL115
MIFTS: 28

Cholestasis, Intrahepatic, of Pregnancy, 3

Categories: Genetic diseases, Reproductive diseases

Aliases & Classifications for Cholestasis, Intrahepatic, of Pregnancy, 3

MalaCards integrated aliases for Cholestasis, Intrahepatic, of Pregnancy, 3:

Name: Cholestasis, Intrahepatic, of Pregnancy, 3 54 13
Cholestasis, Intrahepatic, of Pregnancy 3 29 69
Cholestasis of Pregnancy, Intrahepatic 3 71
Icp3 71

Characteristics:

OMIM:

54
Inheritance:
autosomal dominant
autosomal recessive (rare)

Miscellaneous:
occurs during pregnancy, most often in the third trimester
no chronic or permanent liver damage
see for patients with homozygous abcb4 mutations and unaffected heterozygous family members
oral contraceptives may also cause symptoms
patients with abcb4 mutations benefit from ursodeoxycholic acid (udca) treatment


HPO:

32
cholestasis, intrahepatic, of pregnancy, 3:
Inheritance autosomal recessive inheritance autosomal dominant inheritance


Classifications:



Summaries for Cholestasis, Intrahepatic, of Pregnancy, 3

OMIM : 54
Intrahepatic cholestasis of pregnancy is a reversible form of cholestasis that occurs most often in the third trimester of pregnancy and recurs in 45 to 70% of subsequent pregnancies. Symptoms include pruritus, jaundice, increased serum bile salts, and abnormal liver enzymes, all of which resolve rapidly after delivery. However, the condition is associated with fetal complications, including placental insufficiency, premature labor, fetal distress, and intrauterine death. Women with ICP are also susceptible to oral contraceptive-induced cholestasis (OCIC). Ursodeoxycholic acid (UDCA) is an effective treatment for conditions caused by ABCB4 mutations (summary by Pasmant et al., 2012). Mutation in the ABCB4 gene accounts for about 15% of ICP cases (summary by Ziol et al., 2008). For a discussion of genetic heterogeneity of ICP, see ICP1 (147480). (614972)

MalaCards based summary : Cholestasis, Intrahepatic, of Pregnancy, 3, also known as cholestasis, intrahepatic, of pregnancy 3, is related to gallbladder disease 1 and cholestasis, familial intrahepatic, of pregnancy 3, and has symptoms including jaundice, premature birth and intrahepatic cholestasis. An important gene associated with Cholestasis, Intrahepatic, of Pregnancy, 3 is ABCB4 (ATP Binding Cassette Subfamily B Member 4). The drugs Ursodeoxycholic acid and Metformin have been mentioned in the context of this disorder. Affiliated tissues include liver, small intestine and testes.

UniProtKB/Swiss-Prot : 71 Cholestasis of pregnancy, intrahepatic 3: A liver disorder of pregnancy. It presents during the second or, more commonly, the third trimester of pregnancy with intense pruritus which becomes more severe with advancing gestation and cholestasis. It causes fetal distress, spontaneous premature delivery and intrauterine death. Patients have spontaneous and progressive disappearance of cholestasis after delivery. Cholestasis results from abnormal biliary transport from the liver into the small intestine.

Related Diseases for Cholestasis, Intrahepatic, of Pregnancy, 3

Diseases in the Cholestasis, Intrahepatic, of Pregnancy, 3 family:

Cholestasis, Intrahepatic, of Pregnancy, 1 Cholestasis, Familial Intrahepatic, of Pregnancy 1
Cholestasis, Familial Intrahepatic, of Pregnancy 3

Diseases related to Cholestasis, Intrahepatic, of Pregnancy, 3 via text searches within MalaCards or GeneCards Suite gene sharing:

id Related Disease Score Top Affiliating Genes
1 gallbladder disease 1 10.9
2 cholestasis, familial intrahepatic, of pregnancy 3 10.8

Symptoms & Phenotypes for Cholestasis, Intrahepatic, of Pregnancy, 3

Symptoms via clinical synopsis from OMIM:

54

Prenatal Manifestations- Delivery:
premature delivery
intrauterine fetal death

Abdomen- Liver:
intrahepatic cholestasis during pregnancy, resolves postpartum
abnormal liver function tests during pregnancy, resolves postpartum
hepatic fibrosis seen on biopsy (in some patients)
ductal proliferation seen on biopsy (in some patients)

Skin Nails & Hair- Skin:
pruritus during pregnancy, resolves postpartum
jaundice (in some patients), resolves postpartum

Prenatal Manifestations- Movement:
fetal distress

Laboratory- Abnormalities:
abnormal liver function tests during pregnancy, resolves postpartum
increased serum bile acid concentration during pregnancy, resolves postpartum


Clinical features from OMIM:

614972

Human phenotypes related to Cholestasis, Intrahepatic, of Pregnancy, 3:

32 (show all 6)
id Description HPO Frequency HPO Source Accession
1 jaundice 32 HP:0000952
2 premature birth 32 HP:0001622
3 intrahepatic cholestasis 32 HP:0001406
4 pruritus 32 HP:0000989
5 abnormal liver function tests during pregnancy 32 HP:0200148
6 increased serum bile acid concentration during pregnancy 32 HP:0200150

Drugs & Therapeutics for Cholestasis, Intrahepatic, of Pregnancy, 3

Drugs for Cholestasis, Intrahepatic, of Pregnancy, 3 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 8)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Ursodeoxycholic acid Approved, Investigational Phase 3,Phase 2 128-13-2 31401
2
Metformin Approved Phase 2, Phase 3 657-24-9 14219 4091
3
Metronidazole Approved Phase 2, Phase 3 443-48-1 4173
4 Cholagogues and Choleretics Phase 3,Phase 2
5 Gastrointestinal Agents Phase 3,Phase 2
6 Hypoglycemic Agents Phase 2, Phase 3
7 Liver Extracts Phase 2, Phase 3
8 Estrogens

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Ursodeoxycholic Acid in the Treatment of Intrahepatic Cholestasis of Pregnancy Completed NCT01576458 Phase 3 ursodeoxycholic acid;Placebo
2 Metformin in Intrahepatic Cholestasis of Pregnancy Not yet recruiting NCT03056274 Phase 2, Phase 3 Metformin;Ursodeoxycholic Acid
3 Ursodeoxycholic Acid And Cholestasis Of Pregnancy Withdrawn NCT01226823 Phase 3 Ursodeoxycholic Acid;Placebo
4 ABCB4 Gene Mutations in Intrahepatic Cholestasis of Pregnancy and Controls Completed NCT00700232
5 White Adipose Tissue in Pregnancy Study Recruiting NCT02495987
6 The Use of Fish Oil Supplementation in Treatment of Intrahepatic Cholestasis of Pregnancy Withdrawn NCT01965054

Search NIH Clinical Center for Cholestasis, Intrahepatic, of Pregnancy, 3

Genetic Tests for Cholestasis, Intrahepatic, of Pregnancy, 3

Genetic tests related to Cholestasis, Intrahepatic, of Pregnancy, 3:

id Genetic test Affiliating Genes
1 Cholestasis, Intrahepatic, of Pregnancy 3 29

Anatomical Context for Cholestasis, Intrahepatic, of Pregnancy, 3

MalaCards organs/tissues related to Cholestasis, Intrahepatic, of Pregnancy, 3:

39
Liver, Small Intestine, Testes

Publications for Cholestasis, Intrahepatic, of Pregnancy, 3

Variations for Cholestasis, Intrahepatic, of Pregnancy, 3

UniProtKB/Swiss-Prot genetic disease variations for Cholestasis, Intrahepatic, of Pregnancy, 3:

71
id Symbol AA change Variation ID SNP ID
1 ABCB4 p.Ala546Asp VAR_023503 rs121918441
2 ABCB4 p.Arg150Lys VAR_043081 rs757693457
3 ABCB4 p.Gly762Glu VAR_043099

ClinVar genetic disease variations for Cholestasis, Intrahepatic, of Pregnancy, 3:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 ABCB4 NM_018849.2(ABCB4): c.2869C> T (p.Arg957Ter) single nucleotide variant Pathogenic rs121918440 GRCh37 Chromosome 7, 87041264: 87041264
2 ABCB4 NM_018849.2(ABCB4): c.1712delT (p.Val571Aspfs) deletion Pathogenic rs387906527 GRCh37 Chromosome 7, 87069002: 87069002
3 ABCB4 NM_018849.2(ABCB4): c.1637C> A (p.Ala546Asp) single nucleotide variant Pathogenic rs121918441 GRCh37 Chromosome 7, 87069077: 87069077
4 ABCB4 NM_018849.2(ABCB4): c.1328_1329delAGinsCAA (p.Gln443Profs) indel Pathogenic rs387906528 GRCh37 Chromosome 7, 87072662: 87072663
5 ABCB4 NM_018849.2(ABCB4): c.430C> T (p.Arg144Ter) single nucleotide variant Pathogenic rs72552780 GRCh37 Chromosome 7, 87082366: 87082366

Expression for Cholestasis, Intrahepatic, of Pregnancy, 3

Search GEO for disease gene expression data for Cholestasis, Intrahepatic, of Pregnancy, 3.

Pathways for Cholestasis, Intrahepatic, of Pregnancy, 3

GO Terms for Cholestasis, Intrahepatic, of Pregnancy, 3

Sources for Cholestasis, Intrahepatic, of Pregnancy, 3

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