title: Erythropoietic protoporphyria: a family study and report of a novel mutation in the FECH gene.
abstract: Erythropoietic protoporphyria (EPP) is a rare inherited disorder of heme biosynthesis mostly caused by a deficient activity of the enzyme ferrochelatase (FECH), and consequent accumulation of protoporphyrin (PP) in various tissues. Clinical manifestations include a childhood onset, cutaneous photosensitivity and, sometimes, hepatobiliary disease. We report a 16-year-old male with EPP characterized by acute episodes of painful photosensitivity since early infancy, permanent changes in the photoexposed skin, microcytic anemia, thrombocytopenia, and mild hepatic dysfunction. His 18-year-old sister presented less acute symptoms with no chronic changes. Lesional biopsy disclosed perivascular deposition of PAS positive hyaline material. Rimington-Cripps test was positive and PP erythrocyte levels were >9,000 μg/L (N<1,600), but normal in their parents and younger brother. Genetic studies in both patients and their mother revealed heterozygosity for a novel mutation (c.1052delA) in FECH gene of both children, and heterozygosity for the hypomorphic allele IVS3-48T>C in all of them. This confirms the "pseudodominant" inheritance pattern usually observed, explained by the combined presence of a disabling FECH mutation and a common intronic polymorphism affecting the counterpart allele (IVS3-48T>C). Phenotypic heterogeneity for this genotype explains the divergent clinical presentation. This is the first description of a Portuguese family with EPP characterized at the molecular level.
authors.affiliation: Dermatovenereology Department, Hospital S. João, Alameda Pr. H. Monteiro, 4200-319 Porto, Portugal. paulomoraiscardoso@gmail.com
authors.forename: Paulo
authors.initials: P
authors.lastname: Morais
authors.forename: Alberto
authors.initials: A
authors.lastname: Mota
authors.forename: Teresa
authors.initials: T
authors.lastname: Baudrier
authors.forename: Filipe
authors.initials: F
authors.lastname: Trigo
authors.forename: João Paulo
authors.initials: JP
authors.lastname: Oliveira
authors.forename: Rita
authors.initials: R
authors.lastname: Cerqueira
authors.forename: Aida
authors.initials: A
authors.lastname: Palmeiro
authors.forename: Purificação
authors.initials: P
authors.lastname: Tavares
authors.forename: Filomena
authors.initials: F
authors.lastname: Azevedo
mesh_terms: D000293:Adolescent; D001706:Biopsy; D005260:Female; D005294:Ferrochelatase / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011174:Portugal; D046351:Protoporphyria, Erythropoietic / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*
chemical_list: D005294:Ferrochelatase