Red blood cell protoporphyrins (free protoporphyrin and zinc protoporphyrin)

Free protoporphyrin IX (FPP) is the final intermediate in the heme biosynthesis pathway. In erythroid cells, the enzyme ferrochelatase catalyzes the insertion of iron into protoporphyrin IX to form heme. When iron availability is limited, ferrochelatase can instead incorporate zinc into protoporphyrin IX, forming zinc protoporphyrin (ZPP). Erythropoietic protoporphyria (EPP) results from a partial deficiency of ferrochelatase, leading to marked accumulation of FPP. In contrast, X-linked erythropoietic protoporphyria (XLP) is caused by a gain-of-function mutation in the ALAS2 gene, leading to increased activity of aminolevulinic acid synthase (ALAS), the first enzyme in the heme biosynthesis pathway. This results in significantly elevated levels of both FPP and ZPP. In XLP, ZPP typically constitutes more than 15% of total RBC protoporphyrins. ZPP levels are also elevated in iron deficiency anemia and in chronic lead exposure, where iron incorporation into heme is impaired. Mild to moderate elevations in ZPP may also be observed in sideroblastic anemia, megaloblastic anemia, and hemolytic disorders. Please note, measurement of red blood cell protoporphyrins is not indicated in suspected acute porphryia. Requests for this test when received with clinical details related to suspected acute porphyria will be cancelled as not indicated.