title: Photosensitivity and acute liver injury in myeloproliferative disorder secondary to late-onset protoporphyria caused by deletion of a ferrochelatase gene in hematopoietic cells.
abstract: Late-onset erythropoietic protoporphyria (EPP) is a rare complication of myelodysplastic syndrome (MDS) but has not been described in association with a myeloproliferative disorder (MPD). EPP is normally an inherited disorder characterized by photosensitivity that starts in early childhood and results from overproduction of protoporphyrin secondary to ferrochelatase (FECH) deficiency. Severe liver disease occurs in 1% to 2% of patients. Here we report that severe photosensitivity and cholestatic liver disease in a patient with a myeloproliferative disorder was caused by excess protoporphyrin production from a clone of hematopoietic cells in which one FECH allele had been deleted. Our observations suggest that the usual explanation for the association of late-onset EPP with MPD and MDS is acquired somatic mutation of one FECH allele in bone marrow and show for the first time that the consequent overproduction of protoporphyrin may be severe enough to cause acute liver damage.
authors.affiliation: Department of Dermatology, University Hospital of Wales, Cardiff, United Kingdom.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Goodwin
authors.forename: W Jonathan
authors.initials: WJ
authors.lastname: Kell
authors.forename: Peter
authors.initials: P
authors.lastname: Laidler
authors.forename: C Colin
authors.initials: CC
authors.lastname: Long
authors.forename: Sharon D
authors.initials: SD
authors.lastname: Whatley
authors.forename: Mark
authors.initials: M
authors.lastname: McKinley
authors.forename: Michael N
authors.initials: MN
authors.lastname: Badminton
authors.forename: Alan K
authors.initials: AK
authors.lastname: Burnett
authors.forename: Geraint T
authors.initials: GT
authors.lastname: Williams
authors.forename: George H
authors.initials: GH
authors.lastname: Elder
mesh_terms: D000208:Acute Disease; D017668:Age of Onset; D002779:Cholestasis / Q000209:etiology; D002999:Clone Cells / Q000473:pathology; D005294:Ferrochelatase / Q000235:genetics*; D017353:Gene Deletion; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008107:Liver Diseases / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000150:complications* / Q000235:genetics / Q000473:pathology; D010787:Photosensitivity Disorders / Q000209:etiology*; D046351:Protoporphyria, Erythropoietic / Q000150:complications* / Q000209:etiology / Q000235:genetics*; D011524:Protoporphyrins / Q000096:biosynthesis
chemical_list: D011524:Protoporphyrins; D005294:Ferrochelatase