Porphyria cutanea tarda (PCT) is the most common human porphyria, due to hepatic deficiency of uroporphyrinogen decarboxylase (UROD), which is acquired in the presence of iron overload and various susceptibility factors, such as alcohol abuse, smoking, hepatitis C virus (HCV) infection, HIV infection, iron overload with HFE gene mutations, use of estrogens, and UROD mutation.
Patients with porphyria cutanea tarda (PCT) reveal a susceptibility to reversible inactivation of hepatic uroporphyrinogen decarboxylase, which might be triggered by alcohol, hepatitis C virus infection, and iron overload.
Aryl hydrocarbon receptor ligands, such as polychlorinated biphenyls (PCBs), cause inhibition of the heme biosynthesis enzyme, uroporphyrinogen decarboxylase; this leads to uroporphyria and hepatic tumors, which are markedly enhanced by iron overload in C57BL/10 and C57BL/6 strains of mice.
Mild to moderate iron overload is common in PCT, as iron is one of the factors which trigger the clinical manifestations of the disease through the inactivation of URO-D. A role for genetic hemochromatosis in the development of iron overload in sporadic PCT has been hypothesized in the past.