[From gene to disease; unconjugated hyperbilirubinemia: Gilbert's syndrome and Crigler-Najjar types I and II].
Gilbert's syndrome consists of a mild unconjugated hyperbilirubinemia occurring in the absence of liver disease or haemolysis. Total plasma bilirubin can be as high as 80 mumol/l and mild intermittent jaundice does occur. The inheritance pattern is probably autosomal recessive. It has been estimated that some 10-15% of the Western population suffers from Gilbert's syndrome. Bilirubin-uridinediphosphate-glucuronosyltransferase (UGT1A1) is the only enzyme involved in the conjugation of bilirubin. In patients with Gilbert's syndrome, hepatic glucuronidation by UGT1A1 is reduced to about 30% of normal. In Western populations a variant TATAA element in the upstream promotor region of the UGT1A1 gene is firmly associated with the disease. Crigler-Najjar types I and II are autosomal recessive disorders associated with near (type II) or complete absence (type I) of UGT1A1 enzyme activity. There is a persistent unconjugated hyperbilirubinemia (range 300-850 mumol/l) with the plasma concentrations being higher in type I than in type II. Genetic mutations in exon 1-5 cause both Crigler-Najjar type I and type II.
Drenth
J P H
JP
Universitair Medisch Centrum St Radboud, afd. Maag-, Darm- en Leverziekten, Postbus 9101, 6500 HB Nijmegen. joostphdrenth@cs.com
Peters
W H M
WH
Jansen
J B M J
JB
D001663:Bilirubin / Q000097:blood; D003414:Crigler-Najjar Syndrome / Q000201:enzymology / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic; D005878:Gilbert Disease / Q000201:enzymology / Q000235:genetics*; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism*; D006720:Homozygote; D006801:Humans; D009154:Mutation; D016385:TATA Box
C019787:bilirubin glucuronoside glucuronosyltransferase; D014453:Glucuronosyltransferase; D001663:Bilirubin