title: Advances in understanding the pathogenesis of congenital erythropoietic porphyria.
abstract: Congenital erythropoietic porphyria (CEP) is a rare genetic disease resulting from the remarkable deficient activity of uroporphyrinogen III synthase, the fourth enzyme of the haem biosynthetic pathway. This enzyme defect results in overproduction of the non-physiological and pathogenic porphyrin isomers, uroporphyrin I and coproporphyrin I. The predominant clinical characteristics of CEP include bullous cutaneous photosensitivity to visible light from early infancy, progressive photomutilation and chronic haemolytic anaemia. The severity of clinical manifestations is markedly heterogeneous among patients; and interdependence between disease severity and porphyrin amount in the tissues has been pointed out. A more pronounced endogenous production of porphyrins concomitant to activation of ALAS2, the first and rate-limiting of the haem synthesis enzymes in erythroid cells, has also been reported. CEP is inherited as autosomal recessive or X-linked trait due to mutations in UROS or GATA1 genes; however an involvement of other causative or modifier genes cannot be ruled out.
authors.affiliation: U.O. di Medicina Interna, Fondazione IRCCS Cà Granda - Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Di Pierro
authors.affiliation: U.O. di Medicina Interna, Fondazione IRCCS Cà Granda - Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Brancaleoni
authors.affiliation: U.O. di Medicina Interna, Fondazione IRCCS Cà Granda - Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Granata
mesh_terms: D050982:GATA1 Transcription Factor / Q000235:genetics; D006418:Heme / Q000096:biosynthesis; D006801:Humans; D009154:Mutation; D010641:Phenotype; D017092:Porphyria, Erythropoietic / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011166:Porphyrins / Q000096:biosynthesis / Q000378:metabolism; D014576:Uroporphyrinogen III Synthetase
chemical_list: D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D011166:Porphyrins; D006418:Heme; D014576:Uroporphyrinogen III Synthetase
keywords: GATA1 and ALAS2 genes; UROS; congenital erythropoietic porphyria; haemolytic anaemia; uroporphyrinogen III synthase