Rare genetically transmitted disorder of the
porphyrin-heme in which reduced activity of the enzyme ferrochelatase leads
to accumulation of protoporphyrins in erythrocytes with cutaneous and
Congenital Erythropoietic Protoporphyria; Erythrohepatic
Protoporphyria; Heme Synthetase Deficiency; Protoporphyria.
Mode of inheritance in erythropoietic
protoporphyria (EPP) is complex and can be either autosomal dominant with
low clinical penetrance, as is in most cases, or autosomal recessive. The
gene for human ferrochelatase (FECH) has been mapped to 18q21.3.
The basic defect affects the mitochondrial enzyme
ferrochelatase. The nature of the defect on the molecular level is
uncertain. Protoporphyrin diffuses from the erythrocytes into the plasma to
be bound to albumin and the heme-binding protein hemopexin. Protoporphyrin
deposits in the skin are responsible for the extreme photosensitivity. The
excess porphyrin comes from both erythropoietic and hepatic tissues.
Ultraviolet light photoactivates protoporphyrins that then cause tissue
damage by release of free oxygen radicals, which manifests as
Fluorescence of a significant proportion of red blood
cells is detectable by ultraviolet microscopy because of the presence of
free erythrocyte protoporphyrin. A reduction in the activity of the enzyme
ferrochelatase (also called heme synthase, a mitochondrial enzyme
responsible for the final step in the heme synthesis pathway, which is the
incorporation of ferrous iron into protoporphyrin) to 10 to 25% of normal
levels has been demonstrated. This is unlike the other dominantly inherited
forms of porphyria, in which only a 50% reduction of activity of the
specific enzyme is observed.
Stinging or burning of the skin may result within
1 hour of sun exposure. This is followed by edema and erythema. Solar
urticaria, petechiae, vesicles, purpura, and crustification may develop and
last for several days. Late skin changes include thickening of the skin with
a waxy appearance, shallow pits, and linear creases on the face
(particularly cheeks and nose). Artificial lights, particularly operating
room lamps, may cause photosensitivity. Cholelithiasis is fairly common (in
approximately 30% of patients) and may present at an unusually early age.
Hepatic cholestasis is rare (1-4% of patients) but often has a severe
course. Rarely, hemolytic or mild hypochromic anemia is present, and mild
(nonhemolytic) anemia has been described in up to 25% of cases.
Polyneuropathy and quadriparesis may occur. Excessive protoporphyrin is
excreted in bile, and hence in feces, but not in urine because
protoporphyrin is only poorly water-soluble. It may be deposited in the
liver, resulting in progressive and even fatal liver damage. Management
includes avoidance of exposure to sunlight (ensure that the chosen sunscreen
also protects in the 400-nm range, as common commercial sunscreens often
only effectively block light with a wavelength of approximately 300 nm)
and/or skin protection by parenteral administration of beta-carotene. Liver
disease may be ameliorated by treatment with cholestyramine (to prevent
enterohepatic recirculation of protoporphyrin), activated charcoal, and bile
In general, EPP is considered a
benign disorder with clinical symptoms mainly affecting the skin. Although ...