Table 1
Genetic forms of intrahepatic cholestasis or hyperbilirubinaemia
| Disease | Chromosome | Gene | Defect | Phenotype |
| PFIC type 1 | 18q21 | FIC1, P type ATPase with homology to a putative aminophospholipid translocator | Pathogenetic mechanism unknown | First recurrent, later permanent and progressive cholestasis, no bile duct proliferation, normal gamma-GT, extrahepatic manifestations in some patients |
| BRIC | 18q21 | FIC1 | Unknown but most likely a regulatory defect of bile salt secretion | Recurrent attacks of severe cholestasis, pruritus, jaundice, steatorrhoea, and weight loss. Normal liver function in intervals between the attacks |
| PFIC type 2 | 2q24 | BSEP, bile salt export pump | Deficient canalicular bile salt transport | Progressive cholestasis, no bile duct proliferation, giant cell transformation, lobular and portal fibrosis, normal gamma-GT |
| PFIC type 3 | 7q21 | PGY3 | Deficient canalicular phosphatidylcholine transport | Cholestasis, jaundice less prominent, extensive bile duct proliferation and periportal fibrosis, elevated gamma-GT |
| ICP | e.g. 7q21 heterozygosity | e.g. PGY3 | May be associated with e.g. PFIC type 3 but is also associated with other PFIC types | Cholestasis in third trimester of pregnancy, therapeutic effect of ursodeoxycholic acid, associated with increased fetal loss and prematurity |
| Bile acid synthesis defects | e.g. 8q2.3 | e.g. CYP7B1 | Bile acid synthesis enzyme defects with accumulation of toxic intermediates and deficiency of normal bile acids | Cholestasis since birth, failure to thrive, low to normal gamma-GT |
| Dubin-Johnson syndrome | 10q24 | MRP2/cMOAT, canalicular multispecific organic anion transporter | Deficient canalicular organic anion transport, including that of bilirubin conjugates | Conjugated hyperbilirubinaemia, increased urinary coproporphyrin isomer I, hepatic lysosomal pigment, normal life span |
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PFIC, progressive familial intrahepatic cholestasis; BRIC, benign recurrent intrahepatic cholestasis; ICP, intrahepatic cholestasis of pregnancy; PGY, P-glycoprotein; CYP, cytochrome P-450; gamma-GT, gamma-glutamyltransferase.
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Not mentioned in the table is Aagenaes syndrome (intrahepatic cholestasis with lympoedema)17 since the gene defect underlying this disease is unknown.
