Metabolic fate of exogenous delta-aminolevulinic acid in Dubin-Johnson syndrome.

The underlying mechanism of abnormal urinary distribution of CP isomers in DJS is unknown. We administered ALA to DJS patients and carriers as well as to normal controls, and urinary and biliary porphyrins and plasma bilirubin were studied. In sharp contrast to the remarkable increase in urinary CP-III excretion in normal controls (2234 nmol/gm creatinine during the first 2 hr) after ALA, very small increase was observed in DJS patients (19 nmol). In DJS carriers the increase took intermediate values (1122 nmol). The increments in urinary CP-I were smallest in DJS patients, and the peak of its increase was delayed. These data are compatible with the hypothesis that a carrier-mediated mechanism in transporting CP-gen isomers I and III from the liver cells to the plasma may be anomalous in DJS hepatocytes and that the increased urinary CP-I characteristic of DJS may be the result of a disturbance in the uptake process of CP-gen I, derived mainly from the erythropoietic tissues, by DJS liver cells. Although the biliary percent of CP-I in controls decreased after ALA, it remained unchanged in DJS, suggesting the existence of a bile canalicular barrier against CP-gen-III in DJS. The elevated biliary porphyrins and plasma bilirubin after ALA in DJS patients favor an idea that there may be no major enzymatic derangements in the metabolic sequences from ALA to bilirubin. The increased excretion of PP in DJS bile after ALA remained to be explained.