Specific pattern of unconjugated bilirubin during fasting can identify constitutional hyperbilirubinemia

The pattern of individual bilirubin pigments during a 24 hour caloric restriction (400 Kcal) was investigated in three groups of patients: one group with constitutional hyperbilirubinaemia (n = 29), another with microcytaemia and signs of haemolysis (n = 15) and the third consisting of patients without signs of hepatic disease (n = 11). The different bilirubin fractions (unconjugated, mono- and di-conjugated) were separated as methylated tetrapyrroles by t.l.c. following alkaline methanolysis. In all patients fasting induced an enhancement of the unconjugated bilirubin while the concentration of mono- and di-methyl esters of conjugated bilirubins remained within the normal range. When a pre-fasting concentration of total bilirubin equal to 1.2 mg/dl was used as a discriminating point, two different patterns in the fasting-induced increase in unconjugated bilirubin were identified. An increase of more than 1 mg/dl was found in 30 patients and 28 of these had constitutional hyperbilirubinaemia as diagnosed by exclusion of other disorders. The group with an increase of less than 1 mg/dl was composed of 25 patients, only one of whom had constitutional hyperbilirubinaemia: 14 were affected by microcytaemia and 10 were outpatients without signs of disease. The "fasting-induced increase in unconjugated bilirubin" has a specificity of 78%, a sensitivity of 84% and a positive and negative predictive value of 85 and 76%, respectively, for the diagnosis of constitutional hyperbilirubinaemia.