title: Hemochromatosis and porphyria.
abstract: 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.
authors.affiliation: Department of Medicine and Biochemistry, The Liver-Biliary-Pancreatic Center, University of Massachusetts Medical School, Worcester 01605-2324, USA.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Lambrecht
authors.forename: Herbert L
authors.initials: HL
authors.lastname: Bonkovsky
mesh_terms: D003937:Diagnosis, Differential; D006432:Hemochromatosis / Q000150:complications* / Q000175:diagnosis / Q000628:therapy; D006801:Humans; D018962:Phlebotomy; D017119:Porphyria Cutanea Tarda / Q000175:diagnosis / Q000209:etiology* / Q000628:therapy; D014578:Uroporphyrins / Q000378:metabolism
chemical_list: D014578:Uroporphyrins