Crigler-Najjar syndrome type

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. 

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. 

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... 

Kapitulnik J, Gonzalez FJ. 1992. The role of cytochrome P450 in the elimination of bilirubin in congenital jaundice (Crigler-Najjar syndrome type I). J. Basic Clin. Physiol. Pharmacol. 3 90-91... 

Crigler-Najjar syndrome type I is a rare disorder caused by complete absence of UDP-glucuronyltransferase and manifested by very high levels of unconjugated bilirubin (25 to 50 mg/dL). It is inherited as an autosomal recessive trait. Most patients die of severe brain damage caused by ker-... 

This is a rare autosomal dominant disorder characterized by a partial deficiency of UDP-glucuronyltransferase. Unconjugated bilirubin is usually 5 to 20 mg/dL (85 to 340 Llmol/L). Unlike the Crigler-Najjar syndrome type I, type II responds dramatically to phenobarbital and a normal life can be expected. 

In Crigler-Najjar syndrome type /activity of hepatic bilirubin UDP-glucuronyltransferase is undetectable and bilirubin conjugates are absent from the serum, bile, and urine, but biliary secretion of sulfobromophthalein and indocyanine green is normal. The disease is apparent shortly after birth, kemicterus develops, and death commonly occurs during the neonatal period. The effectiveness of phototherapy is often transient. The enzyme is not inducible by phenobarbital. This autosomal recessive defect occurs in all races. The Gunn strain of Wister rats has a similar genetic defect and has been used to study the syndrome. 

Crigler-Najjar syndrome type II (Arias syndrome) is milder, usually benign, and caused by partial deficiency of bilirubin UDP-glucuronyltransferase. Jaundice may not appear until the second or third decade of life. The monoglucuronide is the predominant pigment in bile. Phenobarbital induces the enzyme. Dominant and recessive inheritance patterns have been described. An accurate diagnosis of type 1, as opposed to type 2 Crigler-Najjar syndrome, is essential since orthotopic liver transplantation is an important therapy for type 1 patients. 

A major complicating factor can be hemolytic anemia such as that of erythroblastosis fetalis caused by Rh incompatibility between mother and child. The hemolysis increases the rate of bilimbin formation, which soon overwhelms the liver and produces severe jaundice and ker-nicterus. Sickle cell anemia has a similar effect. Congenital absence of bilimbin UDP-glucuronyltransferase (Crigler-Najjar syndrome type 1) usually causes a kemictems that is fatal shortly afterbirth. Inhibition of glucuronyltransferase... 

Rela, M., Muiesan, P., Vilca-Melendez, H., Dhawan, A., Baker, A., Mieli-Vergani, G., and Heaton, N. D. (1999) Auxiliary partial orthotopic liver transplantation for Crigler-Najjar syndrome type I. Ann. Surg. 229 (4), 565-569. 

Li, Q., Murphree, S. S., Wilier, S. S., Bolli, R., and French, B. A. (1998) Gene therapy with bilirubin-UDP-glucuronosyltransferase in the Gunn rat model of Crigler-Najjar syndrome type 1. Hum. Gene Ther. 9 (4), 497-505. 

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