Crigler-Najjar

Type I Crigler-Najjar syndrome is a rare autosomal recessive disorder. It is characterized by severe congenital jaundice (serum bilirubin usually exceeds 20 mg/dL) due to mutations in the gene encoding bilirubin-UGT activity in hepatic tissues. The disease is often fatal within the first 15 months of life. Children with this condition have been treated with phototherapy, resulting in some reduction in plasma bilirubin levels. Phenobarbital has no effect on the formation of bilirubin glucuronides in patients with type I Crigler-Najjar syndrome. A liver transplant may be curative. 

J4. Jansen, F. H., Malvaux, P., Heirwegh, K. P. M., and Devriendt, A., Congenital non-hemolytic jaundice Crigler-Najjar syndrome. Biol. Neonatorum 14, 53-61 (1969). 

PBREM, phenobarbital-responsive enhaneer module Gilbert, Gilbert syndrome CN2, Crigler-Najjar syndrome type II. 

Aono S, Yamada Y, Keino Het al. Identification of defect in the genes for bilirubin UDP-glucuronosyl-transferase in a patient with Crigler-Najjar syndrome type II. Biochem Biophys Res Commun 1993 197 1239-1244. 

Costa E. Hematologically important mutations bilirubin UDP-glucuronosyltransferase gene mutations in Gilbert and Crigler-Najjar syndromes. Blood Cells Mol Dis 2006 36(l) 77-80. 

A condition similar to the Crigler-Najjar syndrome, though of only a temporary nature, is neonatal jaundice, which exists when the newborn (especially a... 

Finally, there are hereditary causes of non-conjugated, nonhemolytic hyperbilirubinemias. These are Crigler-Najjar types 1 and 2 and Gilbert s syndrome (discussed in the section on Genetic Diseases of Bilirubin Metabolism). 

The other two diseases related to UGT1A1 are Crigler-Najjar (CN) syndrome types I and II. Many different mutations in UGT1A1 have been identified. CN type I patients express a mutated protein that is essentially devoid of activity. These patients therefore are unable to conjugate bilirubin. Until recently, this condition was lethal in childhood however, now these patients can be treated with phototherapy (discussed in the next section on Photobilirubin) and liver transplantation. Patients with CN type II express a mutated protein that retains some activity. These patients generally respond to phenobarbital, which increases the transcription of UGT1A1. Both CN types I and II are recessive disorders and rare. 

Crigler-Najjar Syndrome Mutations in the UGT1A1 gene... 

UGT1A141 Wild type UGT1AT2 879 del 13 Truncation Deletion 2 CN1 (Crigler-Najjar Type 1)... 

UGT1 A1 7 145 TG Y48SD Missense 5 CN2 Crigler-Najjar Type 2)... 

Deficiency of UGT leads to ineffective esterification of bihrubin, which in turn results in an unconjugated hyperbUirubinaemia. Reduced bilirubin conjugation, as a result of a decreased or absent UGT activity, is found in a number of acquired conditions and inherited diseases, such as Crigler-Najjar syndrome (types I and II) and Gilbert syndrome. Bilirubin-conjugating activity is also very low in the neonatal liver. 

Crigler-Najjar syndrome Dubin-Johnson syndrome... 

Three inherited disorders of bilirubin metabolism are associated with defects in bilirubin UGT-1 activity Gilbert s syndrome, and Crigler-Najjar syndrome types I and II. Dubin-Johnson syndrome is due to a defect in the protein pump that extrudes bilirubin from the hepatocyte... 

Gilbert s syndrome Type 1 Crigler-Najjar syndrome Type II Crigler-Najjar syndrome Dubin-Johnson syndrome Rotor s syndrome... 

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