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European Journal of Dermatology

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Clinical and molecular epidemiology of erythropoietic protoporphyria in Italy Article à paraître

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Auteurs
Antonello Pietrangelo (Gruppo Italiano Porfiria) 1
1 Divisione di Medicina Interna, Centro di riferimento regionale per la diagnosi e la cura delle Porfirie, Policlinico di Modena, Dipartimento di Scienze Medico-Chirurgiche Materno-Infantili e dell’Adulto, Università di Modena e Reggio Emilia
2 Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, U.O. di Medicina Generale–Dipartimento di Scienze Cliniche e Comunità, Università degli studi di Milano
3 Centro per le Porfirie, Istituto San Gallicano- IFO IRCCS, Roma
4 Centro Interregionale di Riferimento per la Porfiria, U.O.C. Nefrologia e Dialisi–IRCSS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG)
5 Centro per le Malattie Rare del metabolismo–Porfirie, Azienda Ospedaliera–Università degli Studi di Padova
6 ASST Spedali Civili di Brescia, UO di Dermatologia, Centro di Fotobiologia e Fotodermatologia
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a These authors contributed equally

Background: Erythropoietic protoporphyria (EPP) is a rare inherited disease associated with heme metabolism, characterized by severe life-long photosensitivity and liver involvement. Objectives: To provide epidemiological data of EPP in Italy. Materials and Methods: Prospective/retrospective data of EPP patients were collected by an Italian network of porphyria specialist centres (Gruppo Italiano Porfiria, GrIP) over a 20-year period (1996-2017). Results: In total, 179 patients (79 females) with a clinical and biochemical diagnosis of EPP were assessed, revealing a prevalence of 3.15 cases per million persons and an incidence of 0.13 cases per million persons/year. Incidence significantly increased after 2009 (due to the availability of alfa-melanotide, which effectively limits skin photosensitivity). Mean age at diagnosis was 28 years, with only 22 patients (12.2%) diagnosed ≤10 years old. Gene mutations were assessed in 173 (96.6%) patients; most (164; 91.3%) were FECH mutations on one allele in association with the hypomorphic variant, c.315-48C, on the other (classic EPP), and nine (5.2%) were ALAS2 mutations (X-linked EPP). Only one case of autosomal recessive EPP was observed. Of the 42 different FECH mutations, 15 are novel, three mutations collectively accounted for 45.9% (75/164) of the mutations (c.215dupT [27.2%], c.901_902delTG [11.5%] and c.67 + 5G > A [7.2%]), and frameshift mutations were prevalent (33.3%). A form of light protection was used by 109/179 (60.8%) patients, and 100 (56%) had at least one α-melanotide implant. Three cases of severe acute liver involvement, requiring OLT, were observed. Conclusions: These data define, for the first time, the clinical and molecular epidemiology of EPP in Italy.