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.

Clinical and molecular epidemiology of erythropoietic protoporphyria in Italy / Ventura, Paolo; Brancaleoni, Valentina; Di Pierro, Elena; Graziadei, Giovanna; Macrì, Annelise; Carmine Guida, Claudio; Nicolli, Annamaria; Teresa Rossi, Maria; Granata, Francesca; Fiorentino, Valeria.; Fustinoni, Silvia; Sala, Raffella; Calzavara Pinton, Piergiacomo; Trevisan, Andrea; Marchini, Stefano; Cuoghi, Chiara; Marcacci, Matteo; Corradini, Elena; Sorge, Fiammetta; Aurizi, Caterina; Grazia Savino, Maria; Cappellini, Maria Domenica; Pietrangelo, Antonello. - In: EUROPEAN JOURNAL OF DERMATOLOGY. - ISSN 1167-1122. - 30:5(2020), pp. 532-540. [10.1684/ejd.2020.3880]

Clinical and molecular epidemiology of erythropoietic protoporphyria in Italy

Paolo Ventura
Writing – Original Draft Preparation
;
Stefano Marchini
Investigation
;
Chiara Cuoghi
Investigation
;
Matteo Marcacci
Investigation
;
Elena Corradini;Maria Domenica Cappellini
Supervision
;
Antonello Pietrangelo
Supervision
2020

Abstract

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.
2020
7-ott-2020
30
5
532
540
Clinical and molecular epidemiology of erythropoietic protoporphyria in Italy / Ventura, Paolo; Brancaleoni, Valentina; Di Pierro, Elena; Graziadei, Giovanna; Macrì, Annelise; Carmine Guida, Claudio; Nicolli, Annamaria; Teresa Rossi, Maria; Granata, Francesca; Fiorentino, Valeria.; Fustinoni, Silvia; Sala, Raffella; Calzavara Pinton, Piergiacomo; Trevisan, Andrea; Marchini, Stefano; Cuoghi, Chiara; Marcacci, Matteo; Corradini, Elena; Sorge, Fiammetta; Aurizi, Caterina; Grazia Savino, Maria; Cappellini, Maria Domenica; Pietrangelo, Antonello. - In: EUROPEAN JOURNAL OF DERMATOLOGY. - ISSN 1167-1122. - 30:5(2020), pp. 532-540. [10.1684/ejd.2020.3880]
Ventura, Paolo; Brancaleoni, Valentina; Di Pierro, Elena; Graziadei, Giovanna; Macrì, Annelise; Carmine Guida, Claudio; Nicolli, Annamaria; Teresa Rossi, Maria; Granata, Francesca; Fiorentino, Valeria.; Fustinoni, Silvia; Sala, Raffella; Calzavara Pinton, Piergiacomo; Trevisan, Andrea; Marchini, Stefano; Cuoghi, Chiara; Marcacci, Matteo; Corradini, Elena; Sorge, Fiammetta; Aurizi, Caterina; Grazia Savino, Maria; Cappellini, Maria Domenica; Pietrangelo, Antonello
File in questo prodotto:
File Dimensione Formato  
ejd-318671-47921-clinical_and_molecular_epidemiology_of_erythropoietic_protoporphyria_in_italy-a.pdf

Open access

Tipologia: Versione pubblicata dall'editore
Dimensione 379.21 kB
Formato Adobe PDF
379.21 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1220839
Citazioni
  • ???jsp.display-item.citation.pmc??? 7
  • Scopus 10
  • ???jsp.display-item.citation.isi??? 10
social impact