title: Homeostasis of iron and hepcidin in erythropoietic protoporphyria.
abstract: BACKGROUND
  Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are genetic abnormalities of heme synthesis that result in excess production of protoporphyrin and that manifest as severe photosensitivity. These disorders are often associated with iron deficiency anaemia (IDA). Our aim was to determine whether hepcidin is increased in EPP/XLP patients, resulting in decreased enteral iron absorption and IDA.
  
  
  METHODS
  Eight subjects with EPP, one with XLP and nine controls had baseline blood and urine samples collected, and thereafter were given oral ferrous sulphate (660 mg). Post-iron blood and urine samples were collected at 2, 4, 6 and 8 h. Blood counts, serum cytokines, ferritin and iron studies were analysed at baseline. Serum iron studies, serum and urine hepcidin, and erythropoietin (Epo) were analysed at baseline and subsequent time points.
  
  
  RESULTS
  At baseline, EPP-XLP subjects had lower mean blood haemoglobin (13·9/15·3 g/dL) and serum ferritin (31·6/115 ng/mL) than controls. Serum iron levels increased markedly in both cohorts. Mean serum and urine hepcidin levels were significantly lower in the EPP-XLP group at 4 and 8 h post-iron (serum - 4 h, 3·79/26·6, 8 h, 5·79/34·6 nM; urine - 4 h, 0·85/2·50, 8 h, 1·44/6·63 nM/mM creatinine). Serum cytokines and Epo were normal and not different between groups.
  
  
  CONCLUSIONS
  We conclude that serum and urine hepcidin are not inappropriately increased in EPP/XLP subjects at baseline and do not increase over time as serum iron increases after oral ferrous sulphate. Levels of serum cytokines and Epo are normal in EPP/XLP. The molecular basis for the iron-deficient phenotype in EPP/XLP remains unknown.
authors.affiliation: The Liver-Biliary-Pancreatic Center, Carolinas HealthCare System, Charlotte, NC, USA.
authors.forename: Krista
authors.identifier: http://orcid.org/0000-0002-6595-4548
authors.initials: K
authors.lastname: Bossi
authors.affiliation: Department of Research, Carolinas HealthCare System, Charlotte, NC, USA.
authors.forename: Jingyun
authors.initials: J
authors.lastname: Lee
authors.affiliation: The Liver-Biliary-Pancreatic Center, Carolinas HealthCare System, Charlotte, NC, USA.|Department of Medicine, Carolinas HealthCare System, Charlotte, NC, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Schmeltzer
authors.affiliation: The Liver-Biliary-Pancreatic Center, Carolinas HealthCare System, Charlotte, NC, USA.|Department of Research, Carolinas HealthCare System, Charlotte, NC, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Holburton
authors.affiliation: The Liver-Biliary-Pancreatic Center, Carolinas HealthCare System, Charlotte, NC, USA.
authors.forename: Gale
authors.initials: G
authors.lastname: Groseclose
authors.affiliation: The Liver-Biliary-Pancreatic Center, Carolinas HealthCare System, Charlotte, NC, USA.|Department of Medicine, Carolinas HealthCare System, Charlotte, NC, USA.
authors.forename: Siddesh
authors.initials: S
authors.lastname: Besur
authors.affiliation: Department of Research, Carolinas HealthCare System, Charlotte, NC, USA.
authors.forename: Sunil
authors.initials: S
authors.lastname: Hwang
authors.affiliation: The Liver-Biliary-Pancreatic Center, Carolinas HealthCare System, Charlotte, NC, USA.|Department of Research, Carolinas HealthCare System, Charlotte, NC, USA.|Department of Medicine, Carolinas HealthCare System, Charlotte, NC, USA.
authors.forename: Herbert L
authors.initials: HL
authors.lastname: Bonkovsky
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D004921:Erythropoietin / Q000378:metabolism; D005293:Ferritins / Q000378:metabolism; D064451:Hepcidins / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D046351:Protoporphyria, Erythropoietic / Q000378:metabolism*
chemical_list: D016207:Cytokines; D064451:Hepcidins; D004921:Erythropoietin; D005293:Ferritins; D007501:Iron
keywords: Anaemia; erythropoietic protoporphyria; erythropoietin; hepcidin; iron; protoporphyrin