title: Increased plasma transferrin, altered body iron distribution, and microcytic hypochromic anemia in ferrochelatase-deficient mice.
abstract: Patients with deficiency in ferrochelatase (FECH), the last enzyme of the heme biosynthetic pathway, experience a painful type of skin photosensitivity called erythropoietic protoporphyria (EPP), which is caused by the excessive production of protoporphyrin IX (PPIX) by erythrocytes. Controversial results have been reported regarding hematologic status and iron status of patients with EPP. We thoroughly explored these parameters in Fechm1Pas mutant mice of 3 different genetic backgrounds. FECH deficiency induced microcytic hypochromic anemia without ringed sideroblasts, little or no hemolysis, and no erythroid hyperplasia. Serum iron, ferritin, hepcidin mRNA, and Dcytb levels were normal. The homozygous Fechm1Pas mutant involved no tissue iron deficiency but showed a clear-cut redistribution of iron stores from peripheral tissues to the spleen, with a concomitant 2- to 3-fold increase in transferrin expression at the mRNA and the protein levels. Erythrocyte PPIX levels strongly correlated with serum transferrin levels. At all stages of differentiation in our study, transferrin receptor expression in bone marrow erythroid cells in Fech(m1Pas) was normal in mutant mice but not in patients with iron-deficiency anemia. Based on these observations, we suggest that oral iron therapy is not the therapy of choice for patients with EPP and that the PPIX-liver transferrin pathway plays a role in the orchestration of iron distribution between peripheral iron stores, the spleen, and the bone marrow.
authors.affiliation: INSERM U773, Paris, France.
authors.forename: Saïd
authors.initials: S
authors.lastname: Lyoumi
authors.forename: Marie
authors.initials: M
authors.lastname: Abitbol
authors.forename: Valérie
authors.initials: V
authors.lastname: Andrieu
authors.forename: Dominique
authors.initials: D
authors.lastname: Henin
authors.forename: Elodie
authors.initials: E
authors.lastname: Robert
authors.forename: Caroline
authors.initials: C
authors.lastname: Schmitt
authors.forename: Laurent
authors.initials: L
authors.lastname: Gouya
authors.forename: Hubert
authors.initials: H
authors.lastname: de Verneuil
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Deybach
authors.forename: Xavier
authors.initials: X
authors.lastname: Montagutelli
authors.forename: Carole
authors.initials: C
authors.lastname: Beaumont
authors.forename: Hervé
authors.initials: H
authors.lastname: Puy
mesh_terms: D000747:Anemia, Hypochromic / Q000097:blood / Q000378:metabolism*; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D002478:Cells, Cultured; D004912:Erythrocytes / Q000378:metabolism*; D005294:Ferrochelatase / Q000235:genetics / Q000378:metabolism*; D064451:Hepcidins; D007501:Iron / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D009928:Organ Specificity; D012333:RNA, Messenger / Q000378:metabolism; D014018:Tissue Distribution; D014168:Transferrin / Q000032:analysis / Q000378:metabolism*
chemical_list: D023181:Antimicrobial Cationic Peptides; C579599:Hamp protein, mouse; D064451:Hepcidins; D012333:RNA, Messenger; D014168:Transferrin; D007501:Iron; D005294:Ferrochelatase