The
porphyrias are disorders that can be inherited and acquired, in which the activities of the
enzymes of the
heme biosynthetic pathway are partially or almost totally deficient. There are 8
enzymes involved in the synthesis of
heme, and, with the exception of the first
enzyme, an enzymatic defect at every step leads to tissue accumulation and excessive excretion of
porphyrins and/or their precursors, such as
delta-aminolevulinic acid and
porphobilinogen. Whereas
heme, the final product of the biosynthetic pathway, is biologically important,
porphyrins and their precursors are not only useless but also toxic.
Porphyrias can be classified as either photosensitive or neurologic, depending on the type of symptoms, but some
porphyrias cause both photosensitive and
neurologic symptoms. Alternatively, they can be classified either hepatic or erythropoietic, depending on the principal site of expression of the specific enzymatic defect. The tissue-specific expression of
porphyrias is largely due to the tissue-specific control of
heme pathway gene expression, particularly at the level of
delta-aminolevulinate synthase, the first and the rate-limiting
enzyme of
heme biosynthesis. In this chapter, hematologic aspects of the
erythropoietic porphyrias will be described. The 3 major
erythropoietic porphyrias are
congenital erythropoietic porphyria (CEP),
hepatoerythropoietic porphyria (HEP) and
erythropoietic protoporphyria (EPP).