IllnessCholestasis, intrahepatic, pregnancy; differential diagnosis

NGS +

[Sanger]

In intrahepatic cholestasis in pregnancy, the release of bile from liver cells is impaired, usually accompanied by itching and possibly slight icterus in the third trimester. Bile flow returns to normal after delivery, but symptoms may recur in subsequent pregnancies. Cholestasis can lead to problems in pregnancy (fetal distress, premature or even stillbirth) and affects 1% of women in (Northern) Europe. Genetic alterations in the ABCB11 or ABCB4 gene may increase a woman's likelihood of developing intrahepatic cholestasis in pregnancy. The ABCB11 gene codes for a bile salt export pump. Alterations in the ABCB11 gene associated with increased estrogen and progesterone levels decrease the function of this pump. The ABCB4 gene encodes a protein that transports phospholipids into the bile. Most women with intrahepatic cholestasis in pregnancy do not have genetic variants in the ABCB11 or ABCB4 genes. Other genetic and environmental factors probably play a role in susceptibility to the disorder, which is inherited in an autosomal dominant manner with reduced penetrance. The DNA diagnostic yield is largely unknown.

Reference: -

• Alias: Byler disease
• Alias: [Progressive] Familial intrahepatic cholestasis, PFIC
• Allelic: Alpha-methylacyl-CoA racemase deficiency (AMAKR)
• Allelic: Bardet-Biedl syndrome 14, modifier of (TMEM67)
• Allelic: Bilirubin, serum level of, QTL1 (UGT1A1)
• Allelic: Bjornstad syndrome (BCS1L)
• Allelic: Citrullinemia, adult-onset type II (SLC25A13)
• Allelic: Deafness, AR 66 (DCDC2)
• Allelic: Deafness, congenital heart defects, posterior embryotoxon (JAG1)
• Allelic: Emphysema due to AAT deficiency (SERPINA1)
• Allelic: Hajdu-Cheney syndrome (NOTCH2)
• Allelic: Heimler syndrome 1 (PEX1)
• Allelic: Heimler syndrome 2 (PEX6)
• Allelic: Hemorrhagic diathesis due to antithrombin Pittsburgh (SERPINA1)
• Allelic: Joubert syndrome 6 (TMEM87)
• Allelic: Joubert syndrome 7 (RPGRIP1L)
• Allelic: Joubert syndrome 9 (CC2D2A)
• Allelic: Mitochondrial complex III deficiency, nuclear type 1 (BCS1L)
• Allelic: Peroxisome biogenesis disorder 1B [NALD/IRD] (PEX1))
• Allelic: Peroxisome biogenesis disorder 3B (PEX12)
• Allelic: Peroxisome biogenesis disorder 4B (PEX6)
• Allelic: Peroxisome biogenesis disorder 7B (PEX26)
• Allelic: RHYNS syndrome (TMEM67)
• Allelic: Spastic paraplegia 5A, AR (CYP7B1)
• Allelic: Tetralogy of Fallot (JAG1)
• Alagille syndrome 1 (JAG1)
• Alagille syndrome 2 (NOTCH2)
• Arthrogryposis, renal dysfunction + cholestasis 1 (VPS33B)
• Arthrogryposis, renal dysfunction + cholestasis 2 (VIPAS39)
• Bile acid synthesis defect, congenital, 1 (HSD3B7)
• Bile acid synthesis defect, congenital, 2 (AKR1D1)
• Bile acid synthesis defect, congenital, 3 (CYP7B1)
• Bile acid synthesis defect, congenital, 4 (AMACR)
• COACH syndrome 1 (TMEM67)
• COACH syndrome 2 (CC2D2A)
• COACH syndrome 3 (RPGRIP1L)
• Cerebrotendinous xanthomatosis (CYP27A1)
• Cholestasis, benign recurrent intrahepatic, 2; Cholestasis, progr. fam. intrahep. 2 (ABCB11)
• Cholestasis, intrahepatic, of pregnancy, 1 (ATP8B1)
• Cholestasis, intrahepatic, of pregnancy; Cholestasis, progressive fam. intrahepatic 3 (ABCB4)
• Cholestasis, progressive familial intrahepatic 1; Cholestasis, benign recurrent intrahepatic ()
• Cholestasis, progressive familial intrahepatic 4 (TJP2)
• Cholestasis, progressive familial intrahepatic 5 (NR1H4)
• Citrullinemia, type II, neonatal-onset (SLC25A13)
• Crigler-Najjar syndrome, type I (UGT1A1)
• Crigler-Najjar syndrome, type II (UGT1A1)
• Deafness, congenital heart defects + posterior embryotoxon (JAG1)
• Dubin-Johnson syndrome (ABCC2)
• Emphysema-cirrhosis, due to AAT deficiency (SERPINA1)
• Fructose intolerance, hereditary (ALDOB)
• GRACILE syndrome (BCS1L)
• Gilbert syndrome (UGT1A1)
• Hyperbilirubinemia, familial transient neonatal (UGT1A1)
• Hypercholanemia, familial (BAAT)
• Hypercholanemia, familial (EPHX1)
• Ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis (CLDN1)
• Meckel syndrome 3 (TMEM67)
• Meckel syndrome 5 (RPGRIP1L)
• Meckel syndrome 6 (CC2D2A)
• Microvillus inclusion disease (MYO5B)
• Nephronophthisis 11 (TMEM67)
• Nephronophthisis 19 (DCDC2)
• Niemann-Pick disease, type C1 (NPC1)
• Niemann-Pick disease, type D (NPC1)
• Niemann-pick disease, type C2 (NPC2)
• Peroxisome biogenesis disorder 1A [Zellweger] (PEX1)
• Peroxisome biogenesis disorder 3A (Zellweger] (PEX12)
• Peroxisome biogenesis disorder 4A (Zellweger] (PEX6)
• Peroxisome biogenesis disorder 7A [Zellweger] (PEX26)
• Sclerosing cholangitis, neonatal (DCDC2)
• Transaldolase deficiency (TALDO)
• Tyrosinemia, type I (FAH)