Table 1.

Biochemical Characteristics of Erythropoietic Protoporphyria (EPP)

Deficient EnzymeEnzyme ActivityErythrocytesUrineStoolOther
Ferrochelatase 1~10%-30% of normal 2Free protoporphyrin: increased 3, 4, 5, 6Protoporphyrins: normalProtoporphyrin: normal or increasedPlasma porphyrins: increased 7, 8
1.

Deficient activity of ferrochelatase (EC 4.99.1.1), encoded by FECH, leads to the systemic accumulation of free protoporphyrin and a markedly lesser amount of zinc-chelated protoporphyrin, particularly in erythroid and hepatic cells.

2.

The assay for the enzyme ferrochelatase is not widely available and is not used for diagnostic purposes.

3.

In EPP, free protoporphyrin levels are elevated significantly as compared to zinc-chelated protoporphyrin.

4.

Many assays for erythrocyte protoporphyrin or "free erythrocyte protoporphyrin" measure both zinc-chelated protoporphyrin and free protoporphyrin. Free protoporphyrin is distinguished from zinc-chelated protoporphyrin by ethanol extraction or HPLC.

5.

Protoporphyrins (usually zinc-chelated protoporphyrin) are also increased in lead poisoning, iron deficiency, anemia of chronic disease, and various hemolytic disorders, as well as in those porphyrias caused by biallelic pathogenic variants (e.g., harderoporphyria), which are more severe than the acute autosomal dominant porphyrias (e.g., hereditary coproporphyria) caused by a heterozygous variant of the same gene (e.g., CPOX).

6.

In X-linked protoporphyria (XLP), resulting from pathogenic gain-of-function variants in exon 11 of ALAS2, both free and zinc-chelated protoporphyrins are increased (see Differential Diagnosis).

7.

Plasma porphyrins of the III-isomer series are usually increased.

8.

Plasma total porphyrins are increased in porphyrias with cutaneous manifestations including EPP. If plasma porphyrins are increased, the fluorescence emission spectrum of plasma porphyrins at neutral pH can be characteristic and can distinguish EPP from other porphyrias. The emission maximum in EPP occurs at 632-634 nm.

From: Erythropoietic Protoporphyria, Autosomal Recessive

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