A 52-year-old man presented to his primary care physician with
blisters and sores on the backs of his hands. Laboratory studies supported a diagnosis of
porphyria cutanea tarda, complicated by the presence of both the C282Y and H63D mutations in the HFE gene, with susequent
iron over-load. This case illustrates the need to understand the pathogenesis of
porphyria cutanea tarda, particularly the role of excess
iron in the overproduction of uroporphyrin.
Iron, by catalyzing the formation of
reactive oxygen species, can enhance uroporphyrin formation by increasing the rate at which uroporphyrinogen is oxidized to urophophyrin.
Iron may also act indirectly to inhibit
uroporphyrinogen decarboxylase activity by enhancing the formation of non-
porphyrin products of porphyrinogen oxidation that are themselves direct inhibitors of the
enzyme. Finally,
iron can act to increase urophorphyrin production by inducing
delta-aminolevulinic acid synthase, thus increasing the amount of
delta-aminolevulinic acid, the precursor to uroporphyrinogen, present in the cell. After the diagnosis, the patient underwent an aggressive series of therapeutic phlebotomies to reduce
iron levels, and gradually the cutaneous manifestations of
porphyria cutanea tarda improved.