SERUM AND BILE BILIRUBIN PIGMENTS IN THE DIFFERENTIAL-DIAGNOSIS OF CRIGLER-NAJJAR-DISEASE

Objective. To differentiate between Crigler-Najjar (CN) disease types 1 and 2.Design. The patterns of serum bilirubins, bile pigment composi tion, and phenobarbital response were studied. Patients. Three infants , affected by high serum unconjugated bilirubin concentrations, previo usly classified as type 1 CN. Methods. Serum and bile bilirubin pigmen t composition, both before and after phenobarbital (FB) treatment, wer e determined by alkaline methanolysis and high-pressure liquid chromat ography. PB was given for at least 3 weeks by oral administration (5 m g/kg bw per day). Results. No diconjugated bilirubin was found either before or after FB treatment in the serum of the three studied infants . In two patients traces of monoconjugated bilirubin were detected bef ore PB therapy, and the ratio of conjugated/total bilirubin (percent) was increased by the PB response. In the third patient, traces of mono conjugated bilirubin appeared only after PB administration. However, t he serum unconjugated bilirubin concentration decreased significantly only in the second patient, following the second cycle of PB treatment , leading to the diagnosis of type 2 CN. The analysis of the methyl es ter derivatives of bile pigments was also performed on bile samples ob tained in two patients by Entero-Test (R) both before and after PB tre atment. An absolute increment in monoesterified bilirubin concentratio n was found after PB administration, although the percent concentratio n increased in one case and decreased in the other. No diesterified bi lirubin was detected in the bile samples. Conclusions. The present res ults show that in types 1 and 2 CN disease it is possible to detect tr aces of monconjugated but not diconjugated bilirubin both in serum and in bile. Whereas PB treatment is effective in slightly increasing the serum monoconjugated bilirubin concentration even in type 1 CN diseas e, the diagnosis of type 1 or 2 is based on finding a substantial decr ease of serum unconjugated bilirubin following PB administration.