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Advances in understanding the pathogenesis of congenital erythropoietic porphyria
Author(s) -
Di Pierro Elena,
Brancaleoni Valentina,
Granata Francesca
Publication year - 2016
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13978
Subject(s) - porphyria , pathogenesis , enzyme , autosomal recessive trait , gene , heme , medicine , immunology , biology , genetics , biochemistry
Summary 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 ALAS 2, 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 GATA 1 genes; however an involvement of other causative or modifier genes cannot be ruled out.