The Liver in Crigler-Najjar Syndrome, Protoporphyria, and Other Metabolic Disorders

The liver may be involved in metabolic disorders in two ways. (i) Due to its critical role in several metabolic pathways, the liver may be the major site of expression of a biochemical abnormality. For example, in Type I Crigler-Najjar syndrome, absence of hepatic bilirubin glucuronyl transferase activity causes severe unconjugated hyperbilirubinemia which invariably leads to death from kernicterus. (ii) The liver may also be structurally damaged by the metabolic disorder. Several patients with protoporphyria have died in hepatic failure due to liver damage caused by protoporphyrin deposition. Numerous other metabolic disorders can be sited in which significant liver involvement occurs. In many of these disorders, there is no effective medical therapy.