PFIC (Progressive Familial Intrahepatic Cholestasis) Type 1 is characterized by a mutation in FIC-1, a gene predicted to encode a P-type ATPase that may be involved in phospholipid translocation. It was previously identified as a clinical entity known as Byler’s disease. Patients with PFIC may have severe cholestasis manifest by intense pruritus, fat malabsorption and fat soluble vitamin deficiencies. PFIC-1 may be associated with extrahepatic manifestations, especially after liver transplantation, since the FIC-1 gene is expressed in many tissues other than the liver.
PFIC (Progressive Familial Intrahepatic Cholestasis) Type 2 is caused by mutations in the gene that codes for the bile salt export pump, or BSEP. Hepatic excretion of bile acids is primarily controlled by BSEP, so severe cholestasis is common in patients with BSEP disease. As BSEP is expressed only in the liver, extrahepatic disease in PFIC-2 is secondary rather than primary.
PFIC (Progressive Familial Intrahepatic Cholestasis) Type 3 is caused by mutations in the MDR3 gene, a flippase that moves phospholipid to the outer leaflet of cell membranes permitting biliary exctretion. Without functional MDR3, bile is deficient in phosphatidylcholine and abnormally caustic. This damages hepatocytes and bile ducts. The abnormal bile also is prone to form gallstones.
*PFIC (Progressive Familial Intrahepatic Cholestasis) Type 4 is the latest diagnosis in the disease class. It is a mutation in the gene TJP2. Out team is currently working on a full overview of this type of mutation. Check back soon for an update!*