Erythropoietic protoporphyria exacerbated by oral iron therapy

Milligan, A.; Graham‐Brown, R.A.C.; Sárkány, I.; Baker, Herman

doi:10.1111/j.1365-2133.1988.tb07102.x

Cited by 58 publications

(32 citation statements)

References 15 publications

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“…Moreover, if iron supplementation is beneficial in EPP, an iron deficit can be assumed. In the medical literature there are conflicting case reports on the effect of iron supplementation on EPP symptoms [4,18,27,31]. In our clinical experience, iron supplementation has consistently exacerbated EPP phototoxic symptoms, although it may improve the general well-being of the patients, increase their hemoglobin concentrations and thus ameliorate their anemia.…”

Section: Discussionmentioning

confidence: 71%

In ferrochelatase-deficient protoporphyria patients, ALAS2 expression is enhanced and erythrocytic protoporphyrin concentration correlates with iron availability

Barman‐Aksözen

Minder

Schubiger

et al. 2015

Blood Cells, Molecules, and Diseases

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Section: Discussionmentioning

confidence: 71%

In ferrochelatase-deficient protoporphyria patients, ALAS2 expression is enhanced and erythrocytic protoporphyrin concentration correlates with iron availability

Barman‐Aksözen

Minder

Schubiger

et al. 2015

Blood Cells, Molecules, and Diseases

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“…However, results of this approach in patients with EPP are contradictory. It has been reported that iron therapy may exacerbate hepatic dysfunction [48,49] whereas in some case reports the correction of iron deficiency has improved EPP [50,51] . Nevertheless, the mechanism of this favorable response to iron therapy remains unknown, so more studies with a significant number of patients are necessary to clarify the role of iron therapy in the medical treatment of EPP.…”

Section: Parenteral Iron and Transfusion Of Erythrocytesmentioning

confidence: 98%

Liver disease and erythropoietic protoporphyria: A concise review

Casanova

Trapero-Marugán²,

Jones³

et al. 2010

WJG

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The porphyries are a group of metabolic disorders characterized by deficiencies in the activity of enzymes involved in the biosynthesis of heme. In erythropoietic protoporphyria (EPP), in the majority of cases an autosomal dominant disease, there is a mutation of the gene that encodes ferrochelatase (FECH). FECH deficiency is associated with increased concentrations of protoporphyrin in erythrocytes, plasma, skin and liver. The prevalence of this inherited disorder oscillates between 1:75 000 and 1:200 000. Clinical manifestations of EPP appear in early infancy upon first exposure to the sun. Nevertheless, approximately 5%-20% of patients with EPP develop liver manifestations. Retention of protoporphyrin in the liver is associated with cholestatic phenomena and oxidative stress that predisposes to hepatobiliary disease of varying degrees of severity, such as cholelithiasis, mild parenchymal liver disease, progressive hepatocellular disease with end-stage liver disease and acute liver failure. Liver damage is the major risk in EPP patients, so surveillance and frequent clinical and biochemical liver follow-up is mandatory. The diagnostic approach consists in detecting increased levels of protoporphyrin, decreased activity of FECH and genetic analysis of the FECH gene. A variety of non-surgical therapeutic approaches have been adopted for the management of EPP associated with liver disease, but none of these has been shown to be unequivocally efficacious. Nevertheless, some may have a place in preparing patients for liver transplantation. Liver transplantation does not correct the constitutional deficiency of FECH. Consequently, there is a risk of recurrence of liver disease after liver transplantation as a result of continuing overproduction of protoporphyrin. Some authors recommend that bone marrow transplantation should be considered in liver allograft recipients to prevent recurrence of hepatic disease.

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“…35,36 Interestingly, in some EPP patients, the disease is exacerbated by oral iron therapy. [37][38][39] In EPP, the erythroid program functions normally except that diminished levels of ferrochelatase result in less than stoichiometric conversion of protoporphyrin to heme. Because anemia is generally not a feature of EPP, it is clear that sufficient levels of heme are eventually synthesized.…”

Section: Org Frommentioning

confidence: 99%

Production and characterization of erythropoietic protoporphyric heterodimeric ferrochelatases

Najahi‐Missaoui

Dailey

2005

Blood

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Mutations resulting in diminished activity of the dimeric enzyme ferrochelatase are a prerequisite for the inherited disorder erythropoietic protoporphyria (EPP). Patients with clinical EPP have only 10% to 30% of normal levels of ferrochelatase activity, and although many patients with EPP have one mutant allele and one "low-expression" normal allele, the possibility remains that, for some, low ferrochelatase activity may result from an EPP mutation that has an impact on both subunits of the wild-type/mutant heterodimer. Here we present data for 12 ferrochelatase wild-type/EPP mutant heterodimers showing that some mutations result in heterodimers with the residual activity anticipated from individual constituents, whereas others result in heterodimers with significantly lower activity than would be predicted. Although the data do not allow an a priori prediction of heterodimeric residual activity based solely on the in vitro activity of EPP homodimers or the position of the mutated residue within ferrochelatase, mutations that affect the dimer interface or [2Fe-2S] cluster have a significantly greater impact on residual activity than would be predicted. These data suggest that some EPP mutations may result in clinically overt EPP in the absence of a low-expression, wild-type allele; this is of potential significance for genetic counseling of patients with EPP. (Blood. 2005;106:1098-1104)

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Erythropoietic protoporphyria exacerbated by oral iron therapy

Cited by 58 publications

References 15 publications

In ferrochelatase-deficient protoporphyria patients, ALAS2 expression is enhanced and erythrocytic protoporphyrin concentration correlates with iron availability

In ferrochelatase-deficient protoporphyria patients, ALAS2 expression is enhanced and erythrocytic protoporphyrin concentration correlates with iron availability

Liver disease and erythropoietic protoporphyria: A concise review

Production and characterization of erythropoietic protoporphyric heterodimeric ferrochelatases

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