The reference OMIM entry for this protein is 177000

Protoporphyria, erythropoietic; epp
Erythrohepatic protoporphyria
Heme synthetase deficiency
Ferrochelatase deficiency

A number sign (#) is used with this entry because erythropoietic protoporphyria can be caused by compound heterozygous or homozygous mutation in the gene encoding ferrochelatase (FECH; 612386) on chromosome 18q21. The disorder most often results from inheritance of a null FECH allele in trans with a low-expression FECH mutation (612386.0015) prevalent in some populations, resembling autosomal dominant inheritance with incomplete penetrance.

DESCRIPTION

Erythropoietic protoporphyria is an inborn error of porphyrin metabolism caused by decreased activity of the enzyme ferrochelatase, the terminal enzyme of the heme biosynthetic pathway, which catalyzes the insertion of iron into protoporphyrin to form heme. EPP is characterized clinically by photosensitivity to visible light commencing in childhood, and biochemically by elevated red cell protoporphyrin levels (Todd, 1994).

CLINICAL FEATURES

Light-sensitive dermatitis commencing in childhood, usually before 10 years of age, is the presenting finding in erythropoietic protoporphyria (Peterka et al., 1965; de Leo et al., 1976). Patients experience itching and burning, and develop erythema even after brief exposure to bright light. Chronic skin changes sometimes occur (Poh-Fitzpatrick, 1978). Herbert et al. (1991) described a second-degree burn of the light-exposed abdominal wall resulting from exposure during liver transplantation. The patient also had severe polyneuropathy with quadriparesis. Although most cases of EPP present in childhood, Henderson et al. (1995) reported a patient who presented at the age of 33 years and cited even older ages at presentation, namely 62 years (Fallon et al., 1989) and 69 years (Murphy et al., 1985). Whereas most EPP patients experience only a painful photosensitivity, a small number develop liver complications, including fatal liver damage, due to the accumulation of excessive amounts of protoporphyrin in the liver (Bloomer et al., 1975; Cripps et al., 1977; Bloomer, 1979). Gallstones pigmented with protoporphyrin have been reported. Both of the British patients of Magnus et al. (1961) and one of the patients of Haeger-Aronsen (1963) were operated on for gallstones at a relatively young age.

BIOCHEMICAL FEATURES

The essential biochemical abnormality in EPP is overproduction of protoporphyrin, as recognized in the original description by Magnus et al. (1961). The normal level of free erythrocyte protoporphyrin (FEP), of up to about 60 microg/dl red cells, may be increased in manifest cases to over 1,000 microg/dl. Fluorescence of a large proportion of red blood cells can also be observed by ultraviolet microscopy even when FEP is little or not increased. The excess porphyrin comes from both erythropoietic and hepatic tissue (Scholnick et al., 1971), leading to the suggestion of an alternative name, erythrohepatic porphyria. Reduction in activity of ferrochelatase to 10 to 25% of normal levels has been demonstrated (Bonkowsky et al., 1975; Bloomer, 1980). This is unlike the dominantly inherited forms of porphyria (121300, 176000, 176100, 176200) in which 50% reduction of activity of the specific enzyme is observed (Romeo, 1977; Meyer and Schmid, 1978). Went and Klasen (1984) found that the average hemoglobin concentration in EPP patients was 1.5 g/100 ml below that for their age- and sex-matched relatives.

PATHOGENESIS

Ohgari et al. (2005) coexpressed human ferrochelatase carrying His- and HA-tags in a tandem fashi ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 177000 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).