Clinical and molecular epidemiology of erythropoietic protoporphyria in Italy

Eur J Dermatol. 2020 Oct 1;30(5):532-540. doi: 10.1684/ejd.2020.3880.


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.

Keywords: X-Link EPP; cutaneous porphyrias; erythropoietic protoporphyria; ferrochelatase; photodermatosis; protoporphyrin.

Publication types

  • Multicenter Study

MeSH terms

  • 5-Aminolevulinate Synthetase / genetics
  • Adult
  • Cross-Sectional Studies
  • Female
  • Ferrochelatase / genetics
  • Genes, Recessive
  • Genes, X-Linked
  • Humans
  • Incidence
  • Italy
  • Male
  • Molecular Epidemiology
  • Mutation
  • Prevalence
  • Prospective Studies
  • Protoporphyria, Erythropoietic / epidemiology*
  • Protoporphyria, Erythropoietic / genetics*
  • Retrospective Studies


  • 5-Aminolevulinate Synthetase
  • ALAS2 protein, human
  • FECH protein, human
  • Ferrochelatase