Familial clustering of heterogeneous chronic unconjugated hyperbilirubinemia

This study concerns the family of a girl affected by type 2 Crigler-Najjar syndrome; a brother and a sister died of kernicterus a few months after birth. The father and two living siblings had moderate unconjugated hyperbilirubinemia. The patient's liver uridine-diphospho-glucuronyl-transferase activity (UDPGT) was markedly reduced. All the family members underwent nicotinic acid (NA) load to test hepatic uptake capacity. This test, and NA half-life were normal in the patient and in her mother, and altered in the other relatives. The extent of the hyperbilirubinemic response to NA load, and of the NA half-life, together with physical examination over a one-year period were in good agreement with the diagnosis of Gilbert's syndrome in the patient's father and siblings. Our conclusion is that different impairments of hepatic handling of organic anions may be present in members of families with non-hemolytic bilirubinemia.