Gilbe's syndrome Gilbe's syndrome is by far the most common inherited disorder of bilirubin metabolism . It is an autosomal recessive trait when caused by a mutation in the promoter region of the gene for UDP-glucuronyl transferase enzyme (UGT1A1), which leads to reduced enzyme expression. It can be inherited in a dominant fashion when there is a missense mutation in the gene. This results in decreased conjugation of bilirubin, which accumulates as unconjugated bilirubin in the blood. The levels of unconjugated bilirubin increase during fasting, as fasting reduces levels of UDP-glucuronyl transferase. Clinical features The typical presentation is with isolated elevation of bilirubin, typically, although not exclusively, in the setting of physical stress or illness. There are no stigmata of chronic liver disease other than jaundice. Increased excretion of bilirubin and hence stercobilinogen leads to normal-coloured or dark stools, and increased urobilinogen excretion causes the urine to turn dark on standing as urobilin is formed. In the presence of haemolysis, pallor due to anaemia and splenomegaly due to excessive reticulo-endothelial activity are usually present. Investigations The plasma bilirubin is usually less than 100 umol/L (~6 mg/ dL) and the LFTs are otherwise normal. There is no bilirubinuria because the hyperbilirubinaemia is predominantly unconjugated. Hepatic histology is normal and liver biopsy is not recommended for the investigation of patients with possible Gilbe's syndrome. The condition is not associated with liver injury and thus has an excellent prognosis, needs no treatment, and is clinically impoant only because it may be mistaken for more serious liver disease . Ref Davidson edition23rd pg 807