Familial intrahepatic progressive cholestasis refers to a heterogeneous group of hereditary liver diseases of childhood, which are caused by disorders of bile acid and bilr lipid transporters. The result is a bile backflow, which is hepatotoxic.
As the cause work mutations in three genes, which is why the disease can be divided into three forms:
PFIC1 and PFIC2 manifest in the first months of life. Main symptoms include jaundice, cholestasis and pruritus. Other signs include diarrhea, dwarfism, increased electrolyte concentration in sweat, sensorineural hearing loss, pancreatitis and hepatic steatosis. The activity of serum gamma-glutamyl transpeptidase is normal.
PFIC3 differs so far that the disease only occurs in later infancy, childhood or adulthood. Serum gamma-glutamyl transpeptidase activity is increased in patients with PFIC3.
The affected genes are involved in all bile-forming hepatocellular transport systems. PFIC1 is associated with mutations in the ATP8B1 gene at the 18q21 locus, which encodes the FIC1 protein. Mutations in the ABCB11 gene at the 2q24 locus encoded by the bile salt export pump BSEP protein cause of PFIC2. In both cases, the mutations trigger a defective secretion of the bile salts.
Defective secretions of bile phospholipids are the cause of PFIC3. Responsible for this are mutations in the ABCB4 gene at the locus 7q21, which encodes the MDR3 protein.
The prognosis of patients is unfavorable, as they usually develop liver fibrosis with terminal liver failure before reaching adulthood.