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. 2022 Mar 3:13:841050.
doi: 10.3389/fphys.2022.841050. eCollection 2022.

Microcytosis in Erythropoietic Protoporphyria

Giovanna Graziadei  1 , Lorena Duca  1 , Francesca Granata  1 , Giacomo De Luca  2 , Anna De Giovanni  1 , Valentina Brancaleoni  1 , Isabella Nava  1 , Elena Di Pierro  1
Affiliations

Microcytosis in Erythropoietic Protoporphyria

Giovanna Graziadei et al. Front Physiol. .

Abstract

Partial deficiency of the last enzyme of the heme biosynthetic pathway, namely, ferrochelatase (FECH), is responsible for erythropoietic protoporphyria (EPP) in humans. This disorder is characterized by painful skin photosensitivity, due to excessive protoporphyrin IX (PPIX) production in erythrocytes. Although several papers report the presence of iron deficiency anemia in about 50% of EPP patients, there is still no a conclusive explanation of the why this occurs. In the present work, we explored hematological indices and iron status in 20 unrelated Italian EPP patients in order to propose a new hypothesis. Our data show that microcytosis is present in EPP patients also in the absence of anemia and iron deficiency with a link between PPIX accumulation and reduced MCV, probably indicating an indirect condition of heme deficiency. Patients studied had a downward shift of iron parameters due to increased hepcidin concentrations only in a state of repleted iron stores. Interestingly, hemoglobin synthesis was not limited by iron supply except in cases with further iron loss, in which concomitantly increased soluble transferrin (Tf) receptor (sTfR) levels were detected. The mechanisms involved in the iron uptake downregulation in EPP remain unclear, and the role of PPIX accumulation in microcytosis.

Keywords: PPIX accumulation; anemia; erythropoietic protoporphyria; hepcidin; iron and heme deficiency; microcytosis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
sTfR and hepcidin measurements. (A) sTfR distributions in EPP patients compared to healthy subjects (CTRL); (B) hepcidin distributions in EPP patients compared to healthy subjects (CTRL). **p < 0.01, ns = not significant.
Figure 2
Figure 2
Mean values comparison. (A) Hematological and iron status parameters in microcytic and normocytic females compared to Controls (B) Hematological and iron status parameters in microcytic and normocytic males compared to Controls. Hemoglobin [Hb], serum Tf receptor [sTfR], Tf saturation [%SAT].
Figure 3
Figure 3
Hepcidin vs. iron parameter correlations.
See this image and copyright information in PMC

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