title: Inducing iron deficiency improves erythropoiesis and photosensitivity in congenital erythropoietic porphyria.
abstract: Congenital erythropoietic porphyria (CEP) is an autosomal recessive disorder of heme synthesis characterized by reduced activity of uroporphyrinogen III synthase and the accumulation of nonphysiologic isomer I porphyrin metabolites, resulting in ineffective erythropoiesis and devastating skin photosensitivity. Management of the disease primarily consists of supportive measures. Increased activity of 5-aminolevulinate synthase 2 (ALAS2) has been shown to adversely modify the disease phenotype. Herein, we present a patient with CEP who demonstrated a remarkable improvement in disease manifestations in the setting of iron deficiency. Hypothesizing that iron restriction improved her symptoms by decreasing ALAS2 activity and subsequent porphyrin production, we treated the patient with off-label use of deferasirox to maintain iron deficiency, with successful results. We confirmed the physiology of her response with marrow culture studies.
authors.affiliation: Department of Medicine, Division of Hematology, University of Washington, Seattle, WA; and.
authors.forename: Daniel N
authors.identifier: http://orcid.org/0000-0002-0173-5194
authors.initials: DN
authors.lastname: Egan
authors.affiliation: Department of Medicine, Division of Hematology, University of Washington, Seattle, WA; and.
authors.forename: Zhantao
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Medicine, Division of Hematology, University of Utah, Salt Lake City, UT.
authors.forename: John
authors.initials: J
authors.lastname: Phillips
authors.affiliation: Department of Medicine, Division of Hematology, University of Washington, Seattle, WA; and.
authors.forename: Janis L
authors.initials: JL
authors.lastname: Abkowitz
mesh_terms: D000328:Adult; D001565:Benzoates / Q000627:therapeutic use*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002478:Cells, Cultured; D000077588:Deferasirox; D004920:Erythropoiesis / Q000187:drug effects*; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007223:Infant; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D000090463:Iron Deficiencies; D008027:Light / Q000009:adverse effects; D056687:Off-Label Use; D017092:Porphyria, Erythropoietic / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011836:Radiation Tolerance / Q000187:drug effects*; D035781:Siblings; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D000077588:Deferasirox