ABSTRACT
Human protoporphyria results from mutations in the ferrochelatase gene. Heritable
deficiency of ferrochelatase causes overproduction of protoporphyrin IX, principally
in the erythron. Photosensitivity is a universal feature of protoporphyria but hepatic
clearance of the hydrophobic protoporphyrin molecule with excretion in bile may lead
to precipitation within biliary pathways. Thus cholestatic injury and protoporphyrin
gallstones occur. Minor hepatic abnormalities are frequent, but at least 30 patients
have been reported with a progressive liver disease that requires transplantation.
Fulminant hepatic disease appears to be recessively inherited in some pedigrees. Hazards
of liver transplantation include tissue photolysis, hemolysis, and an unexplained
neurological syndrome, but most of the 15 patients reported after transplantation
have survived for several months to >6 years. Aspects of protoporphyria, its pathogenesis
and contemporary therapeutic strategies are considered, with emphasis on hepatic sequelae.
KEY WORDS
protoporphyrin - hepatopathy - cholestasis - liver failure
