Van gen naar ziekte; ongeconjugeerde hyperbilirubinemie: Het syndroom van Gilbert en van Crigler-Najjar type I en 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 μmol/1 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 μmol/1) 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.