Hepatic complications of erythropoietic protoporphyria

Abstract

Erythropoietic protoporphyria (EPP) is caused by mutations in ferrochelatase (<i>FECH</i>), the last step in the haem biosynthesis pathway. EPP is inherited in a pseudodominant fashion, most commonly due to presence of a low-expression splicing variant IVS3-48C <i>in trans</i> to a disease causing mutation. Reduction in fer-rochelatase activity leads to accumulation of protoporphyrin IX (PPIX) and photosensitivity. Hepatotoxicity is a rare complication of EPP, seen in 1–5% of patients.¹ Here we present the first reported case of fatal liver failure secondary to EPP in New South Wales, Australia. The patient was found to carry a known mutation (p.Phe260Leu), but IVS3–48C was not detected. The search for additional modifier genes at the genomic level found several potential candidates. These modifier genes may provide an insight on genotype-phenotype correlations in porphyrias.