Table 1.

Biochemical Characteristics of X-Linked Protoporphyria (XLP)

Enzyme
Defect		Enzyme
Activity		ErythrocytesUrineStoolOther
Erythroid-specific 5-aminolevulinate synthase 2 (ALAS2)>100% of normal 1Free protoporphyrin/
zinc-chelated protoporphyrin ratio 90:10 to 50:50 2, 3, 4		Protoporphyrins not detectableProtoporphyrin normal or ↑Plasma porphyrins ↑ 5
1.

Increased enzyme activity is due to ALAS2 pathogenic gain-of-function variants in exon 11. Note: Lymphocyte ferrochelatase activity is normal.

2.

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.

3.

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).

4.

In erythropoietic protoporphyria, free protoporphyrin levels are elevated significantly as compared to zinc-chelated protoporphyrin (see Differential Diagnosis).

5.

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

From: X-Linked Protoporphyria

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