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
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, U.O. di Medicina Generale–Dipartimento di Scienze Cliniche e Comunità, Università degli studi di Milano
Centro per le Porfirie, Istituto San Gallicano- IFO IRCCS, Roma
Centro Interregionale di Riferimento per la Porfiria, U.O.C. Nefrologia e Dialisi–IRCSS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG)
Centro per le Malattie Rare del metabolismo–Porfirie, Azienda Ospedaliera–Università degli Studi di Padova
ASST Spedali Civili di Brescia, UO di Dermatologia, Centro di Fotobiologia e Fotodermatologia
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. Objective: To provide epidemiological data of EPP in Italy. Materials & 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. Conclusion: These data define, for the first time, the clinical and molecular epidemiology of EPP in Italy.