Chronic hyperbilirubinemia associated with hepatic uptake and storage impairment. A new syndrome resembling that of the mutant Southdown sheep.

A 19-year-old female complained of moderate jaundice since early childhood, without any other clinical abnormality. Apart from the hyperbilirubinemia (which comprised around 50% of conjugated bilirubin), usual hepatic function tests were normal. Oral cholecystogram showed a delayed opacification of a normal gallbladder. Liver histology and hepatic bilirubin UDP-glucuronyltransferase activity were normal. The plasma disappearance rates of bromosulfophthalein, dibromosulfopthalein, rose bengal, and indocyanine green were dramatically reduced. There was a marked impairment of the relative storage capacities of bromosulfophthalein and dibromosulfophthalein; this reduction was associated with, and thought to be the cause of, some decrease of the biliary transport maximum. This new form of chronic benign hyperbilirubinemia seems therefore primarily due to a defect of hepatic uptake and storage, and closely resembles the disease observed in the mutant Southdown sheep. Since it is not yet possible to quantify the Y- and Z-proteins from a needle biopsy of human liver, their role in the pathogenesis of the present disease remains speculative.