A NEW VARIANT OF ERYTHROPOIETIC PROTOPORPHYRIA WITH NORMAL FERROCHELATASE ACTIVITY

Erythropoietic protoporphyria (EPP) in most patients is associated with raised erythrocyte protoporphyrin (PP) levels,  ferrochelatase (FECH) activity < 30% of normal and a combination of an inactivating mutation in the FECH gene with a less active allele, or compound heterozygosity for two inactivating mutations. We recently identified a mother and son with the classic EPP skin symptoms and raised PP levels who have normal FECH activity in lymphoblastoid cells. A 52 year old woman has had complaints of painful erythema and swelling after brief sun exposure since late childhood. Her parental grandmother and an aunt had been photosensitive. Her 23-year-old son has had the same symptoms from the age of 2 years. Both mother and son had raised erythrocyte PP levels, but in contrast to classic EPP they also had raised Zinc PP levels and normal FECH activity levels on three occasions. The mother, but not the son, also had markers of iron deficiency with a low serum iron, high ferritin and high transferrin. Erythrocyte porphobilinogen deaminase levels were increased in both, whereas uroporphyrinogen decarboxylase and protoporphyrinogen oxidase levels were normal (see table). No mutations were detected in the exons, flanking intron regions or mitochondrial targeting region of the FC gene, nor in the iron responsive element of the erythrocyte aminolevulinic acid synthase gene.

In conclusion, this family appears to have a variant of EPP, presenting with similar photosensitivity and raised PP levels, but differing from classic EPP in having normal lymphoblastoid FECH activity and in addition to PP, raised Zinc PP levels. When associated with iron deficiency the PP and ZnPP levels increase further and raised ALA levels are found. The underlying molecular genetic mechanism remains to be determined.