Erythropoietic porphyrias are caused by enzymatic dysfunctions in the
heme biosynthetic pathway, resulting in
porphyrins accumulation in red blood cells. The
porphyrins deposition in tissues, including the skin, leads to photosensitivity that is present in all
erythropoietic porphyrias. In the bone marrow,
heme synthesis is mainly controlled by intracellular labile
iron by post-transcriptional regulation: translation of ALAS2
mRNA, the first and rate-limiting
enzyme of the pathway, is inhibited when
iron availability is low. Moreover, it has been shown that the expression of
ferrochelatase (FECH, an
iron-
sulfur cluster
enzyme that inserts
iron into
protoporphyrin IX to form
heme), is regulated by intracellular
iron level. Accordingly, there is accumulating evidence that
iron status can mitigate disease expression in patients with
erythropoietic porphyrias. This article will review the available clinical data on how
iron status can modify the symptoms of
erythropoietic porphyrias. We will then review the modulation of
heme biosynthesis pathway by
iron availability in the erythron and its role in
erythropoietic porphyrias physiopathology. Finally, we will summarize what is known of FECH interactions with other
proteins involved in
iron metabolism in the mitochondria.