Sources of bile pigment overproduction in Gilbert's syndrome: studies with non-radioactive bilirubin kinetics and with delta-[3,5-3H]aminolaevulinic acid and [2-14C]glycine.
1. The kinetics of non-radioactive bilirubin were investigated in 100 patients with chronic non-haemolytic unconjugated hyperbilirubinaemia and in nine normal volunteers. 2. The patients with Gilbert's syndrome were divided on the basis of a two-compartment model into two distinct groups: group 1 (74 patients) with decreased hepatic uptake and conjugation of bilirubin and a bilirubin turnover rate within the normal range, and group 2 (26 patients) having normal uptake, impaired conjugation and increased bilirubin turnover rate. 3. On the basis of these findings, studies were made of early pigment production in four patients of group 1, in six patients of group 2 and in four of the normal volunteers, with [14C]glycine and delta-[3H]aminolaevulinic acid. 4. After receiving injections of labelled haem precursors, the four patients in group 1 had a normal rate of incorporation of both tracers, whereas abnormalities in incorporation were found in group 2. Four patients showed an increase of the first component of the early peak of [14C]bilirubin as well as of the early peak of [3H]bilirubin, suggesting an increased turnover of hepatic haem. Two patients showed an increased incorporation of [14C]glycine characterized by the fusion of the two early peaks, whereas the incorporation of the delta-[3H]aminolaevulinic acid was normal, indicating the presence of a primary shunt hyperbilirubinaemia. 5. The results confirm that Gilbert's syndrome is a heterogeneous condition with respect to bilirubin turnover rate. The population of Gilbert's syndrome with increased bilirubin turnover rate comprises not only patients with an increased haem erythroid turnover, but also patients with increased metabolism of non-erythroid haem protein in the liver.
D000293:Adolescent; D000328:Adult; D000622:Aminolevulinic Acid / Q000378:metabolism; D001663:Bilirubin / Q000378:metabolism*; D005260:Female; D005878:Gilbert Disease / Q000378:metabolism*; D005998:Glycine / Q000378:metabolism; D006801:Humans; D006933:Hyperbilirubinemia, Hereditary / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male
D000622:Aminolevulinic Acid; D001663:Bilirubin; D005998:Glycine