Iron overload in porphyria cutanea tarda

Background and Objective. Porphyria cutanea tarda (PCT) is a disorder of po rphyrin metabolism associated with decreased activity of uroporphyrinogen d ecarboxylase (URO-D) in the liver. The relevance of iron in the pathogenesi s of PCT is well established: iron overload is one of the factors that trig ger the clinical manifestations of the disease and iron depletion remains t he cornerstone of therapy for PCT, A role for genetic hemochromatosis in th e pathogenesis of iron overload in PCT has been hypothesized in the past bu t only after the recent identification of the genetic defect causing hemoch romatosis has the nature of this association been partially elucidated. Thi s review will outline current concepts of the pathophysiology of iron overl oad in PCT as well as recent contributions to the molecular epidemiology of hemochromatosis defects in PCT. Evidence and Information Sources. The authors of the present review have a long-standing interest in the pathogenesis, etiology acid epidemiology of i ron overload syndromes. Evidence from journal articles covered by the Scien ce Citation index(R) acid Medline(R) has been reviewed and collated with pe rsonal data and experience. State of the Art and Perspectives. Mild to moderate iron overload plays a k ey role in the pathogenesis of PCT, The recent identification of genetic mu tations of the hemochromatosis gene (HFE) in the majority of patients with PCT confirms previous hypotheses on the association between PCT and hemochr omatosis, allows a step forward in the understanding of the pathophysiology of the disturbance of iron metabolism in the liver of PCT patients, and pr ovides an easily detectable genetic marker which could have a useful clinic al application. Besides the epidemiological relevance of the association be tween PCT and hemochromatosis, however, it remains to be fully understood h ow iron overload, and in particular the cellular modifications of the iron status secondary to hemochromatosis mutations, affect the activity of URO-D , and how the altered iron metabolism interacts with the other two common t riggers for PCT and etiological agents for the associated liver disease: al cohol and hepatitis viruses. The availability of a genetic marker for hemoc hromatosis will allow some of these issues to be addressed by studying aspe cts of porphyrins and iron metabolism in liver samples obtained from patien ts with PCT, liver disease of different etiology and different HFE genotype s, and by In vitro studies on genotyped cells and tissues. (C) 1999 Ferrata Storti Foundation.