Crigler – Najjar syndrome is a rare autosomal recessive genetic disorder caused due to defects in bilirubin metabolism.
Synonym: congenital nonhemolytic jaundice
Type I: disease associated with neurological impairment due to bilirubin encephalopathy and jaundice resulting in kernicterus. It is caused by mutation in the uridine diphosphate glucuronosyltransferase gene (UBT1A1) that is responsible for conjugation of bilirubin. The abnormal protein thus produced leads to a very low bilirubin activity.
Clinical manifestations and diagnosis of type I
Type I disease is suspected in neonates who develops persistent jaundice due to unconjugated bilirubin. Some patients have neurological dysfunctions due to kernicterus. It is characterized by hyperbilirubinemia ranging from 20 – 25 mg/dL.
It can be distinguished from hyperbilirubinemia due to hemolytic disorders as they alone do not raise serum bilirubin levels more than 8 mg/dL.
Treatment of type I
- Phototherapy: phototherapy is a widely used method to treat hyperbilirubinemia in newborns. It is less effective in adults as the skin becomes thick.
- Plasmapheresis: as bilirubin is tightly bound to albumin, the removal requires plasmapheresis.
- Calcium phosphate supplementation: oral calcium phosphate can trap unconjugated bilirubin thus lowering serum bilirubin levels.
- Orlistat: orlistat is a lipase inhibitor that traps the intestinal unconjugated bilirubin. In adults it is given in an initial dose of 120 mg three times daily.
- Liver transplantation: to limit the progression into kernicterus.
- Hepatocyte transplantation
- Gene therapy: a normal UGT gene can be administered by autologous cell transplantation.
Type II: disease of low serum bilirubin levels with no neurological impairment. Also known as Arias syndrome.
Clinical manifestations of type II
It is usually found in neonates, associated with jaundice and develops into kernicterus within one year. Cholestasis is also noted.
Serum bilirubin concentration is not as high as type I disease. It usually ranges from 8 – 18 mg/dL. Unconjugated hyperbilirubinemia confirms type II disease.
Treatment of type II
Phenobarbital: 60 – 180 mg/dL daily
Clofibrate: a less side effects are seen
Distinguishing Type I and Type II
- Administration of phenobarbital helps in differential diagnosis as serum bilirubin concentration of type II are decreased with phenobarbital administration but not in type I. the dose of phenobarbital used is 60 to 120 mg for 14 days.
- A significant amount of conjugated bilirubin is found in the bile of type II patients while only a small amount is only detectable in the bile of type I patients.