A pilot study of oral iron therapy in erythropoietic protoporphyria and X-linked protoporphyria
The use of iron supplementation for anemia in erythropoietic protoporphyria (EPP) is controversial with both benefit and deterioration reported in single case reports. There is no systematic study to evaluate the benefits or risks of iron supplementation in these patients. We assessed the potential...
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Elsevier
2022-12-01
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| Series: | Molecular Genetics and Metabolism Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214426922000994 |
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| author | Manisha Balwani Hetanshi Naik Jessica R. Overbey Herbert L. Bonkovsky D. Montgomery Bissell Bruce Wang John D. Phillips Robert J. Desnick Karl E. Anderson |
| author_facet | Manisha Balwani Hetanshi Naik Jessica R. Overbey Herbert L. Bonkovsky D. Montgomery Bissell Bruce Wang John D. Phillips Robert J. Desnick Karl E. Anderson |
| author_sort | Manisha Balwani |
| collection | DOAJ |
| description | The use of iron supplementation for anemia in erythropoietic protoporphyria (EPP) is controversial with both benefit and deterioration reported in single case reports. There is no systematic study to evaluate the benefits or risks of iron supplementation in these patients. We assessed the potential efficacy of oral iron therapy in decreasing erythrocyte protoporphyrin (ePPIX) levels in patients with EPP or X-linked protoporphyria (XLP) and low ferritin in an open-label, single-arm, interventional study. Sixteen patients (≥18 years) with EPP or XLP confirmed by biochemical and/or genetic testing, and serum ferritin ≤30 ng/mL were enrolled. Baseline testing included iron studies, normal hepatic function, and elevated plasma porphyrins and ePPIX levels. Oral ferrous sulfate 325 mg twice daily was administered for 12 months. The primary efficacy outcome was the relative difference in total ePPIX level between baseline and 12 months after starting treatment with iron. Secondary measures included improvement in serum ferritin, plasma porphyrins, and clinical symptoms. Thirteen patients had EPP (8 females, 5 males) and 3 had XLP (all females) and the mean age of participants was 38.8 years (SD 14.5). Ten patients completed all study visits limiting interpretation of results. In EPP patients, a transient increase in ePPIX levels was observed at 3 months in 9 of 12 (75%) patients. Iron was discontinued in 2 of these patients after meeting the protocol stopping rule of a 35% increase in ePPIX. Seven patients withdrew before study end. Ferritin levels increased on iron replacement indicating an improvement in iron status. A decrease in ePPIX was seen in both XLP patients who completed the study (relative difference of 0.67 and 0.5 respectively). No substantial changes in ePPIX were seen in EPP patients at the end of the study (n = 8; median relative difference: -0.21 (IQR: −0.44, 0.05). The most common side effects of iron treatment were gastrointestinal symptoms. Hepatic function remained normal throughout the study. Our study showed that oral iron therapy repletes iron stores and transiently increases ePPIX in some EPP patients, perhaps due to a transient increase in erythropoiesis, and may decrease ePPIX in XLP patients. Further studies are needed to better define the role of iron repletion in EPP.Trial registration: NCT02979249. |
| first_indexed | 2024-04-11T06:28:11Z |
| format | Article |
| id | doaj.art-46347898d81d43eaac3445c801bbcb85 |
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| issn | 2214-4269 |
| language | English |
| last_indexed | 2024-04-11T06:28:11Z |
| publishDate | 2022-12-01 |
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| spelling | doaj.art-46347898d81d43eaac3445c801bbcb852022-12-22T04:40:15ZengElsevierMolecular Genetics and Metabolism Reports2214-42692022-12-0133100939A pilot study of oral iron therapy in erythropoietic protoporphyria and X-linked protoporphyriaManisha Balwani0Hetanshi Naik1Jessica R. Overbey2Herbert L. Bonkovsky3D. Montgomery Bissell4Bruce Wang5John D. Phillips6Robert J. Desnick7Karl E. Anderson8Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Corresponding author at: Department of Genetics and Genomic Sciences, One Gustave L. Levy Place, Box 1497, New York, NY 10029, USA.Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USADepartment of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USAWake Forest NC Baptist Medical Center, Winston-Salem, NC, USADepartment of Medicine, University of California, San Francisco, CA, USADepartment of Medicine, University of California, San Francisco, CA, USADepartment of Internal Medicine, University of Utah, Salt Lake City, UT, USADepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USADepartment of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USAThe use of iron supplementation for anemia in erythropoietic protoporphyria (EPP) is controversial with both benefit and deterioration reported in single case reports. There is no systematic study to evaluate the benefits or risks of iron supplementation in these patients. We assessed the potential efficacy of oral iron therapy in decreasing erythrocyte protoporphyrin (ePPIX) levels in patients with EPP or X-linked protoporphyria (XLP) and low ferritin in an open-label, single-arm, interventional study. Sixteen patients (≥18 years) with EPP or XLP confirmed by biochemical and/or genetic testing, and serum ferritin ≤30 ng/mL were enrolled. Baseline testing included iron studies, normal hepatic function, and elevated plasma porphyrins and ePPIX levels. Oral ferrous sulfate 325 mg twice daily was administered for 12 months. The primary efficacy outcome was the relative difference in total ePPIX level between baseline and 12 months after starting treatment with iron. Secondary measures included improvement in serum ferritin, plasma porphyrins, and clinical symptoms. Thirteen patients had EPP (8 females, 5 males) and 3 had XLP (all females) and the mean age of participants was 38.8 years (SD 14.5). Ten patients completed all study visits limiting interpretation of results. In EPP patients, a transient increase in ePPIX levels was observed at 3 months in 9 of 12 (75%) patients. Iron was discontinued in 2 of these patients after meeting the protocol stopping rule of a 35% increase in ePPIX. Seven patients withdrew before study end. Ferritin levels increased on iron replacement indicating an improvement in iron status. A decrease in ePPIX was seen in both XLP patients who completed the study (relative difference of 0.67 and 0.5 respectively). No substantial changes in ePPIX were seen in EPP patients at the end of the study (n = 8; median relative difference: -0.21 (IQR: −0.44, 0.05). The most common side effects of iron treatment were gastrointestinal symptoms. Hepatic function remained normal throughout the study. Our study showed that oral iron therapy repletes iron stores and transiently increases ePPIX in some EPP patients, perhaps due to a transient increase in erythropoiesis, and may decrease ePPIX in XLP patients. Further studies are needed to better define the role of iron repletion in EPP.Trial registration: NCT02979249.http://www.sciencedirect.com/science/article/pii/S2214426922000994Erythropoietic protoporphyriaX-linked protoporphyriaPhotosensitivityClinical trialIron |
| spellingShingle | Manisha Balwani Hetanshi Naik Jessica R. Overbey Herbert L. Bonkovsky D. Montgomery Bissell Bruce Wang John D. Phillips Robert J. Desnick Karl E. Anderson A pilot study of oral iron therapy in erythropoietic protoporphyria and X-linked protoporphyria Molecular Genetics and Metabolism Reports Erythropoietic protoporphyria X-linked protoporphyria Photosensitivity Clinical trial Iron |
| title | A pilot study of oral iron therapy in erythropoietic protoporphyria and X-linked protoporphyria |
| title_full | A pilot study of oral iron therapy in erythropoietic protoporphyria and X-linked protoporphyria |
| title_fullStr | A pilot study of oral iron therapy in erythropoietic protoporphyria and X-linked protoporphyria |
| title_full_unstemmed | A pilot study of oral iron therapy in erythropoietic protoporphyria and X-linked protoporphyria |
| title_short | A pilot study of oral iron therapy in erythropoietic protoporphyria and X-linked protoporphyria |
| title_sort | pilot study of oral iron therapy in erythropoietic protoporphyria and x linked protoporphyria |
| topic | Erythropoietic protoporphyria X-linked protoporphyria Photosensitivity Clinical trial Iron |
| url | http://www.sciencedirect.com/science/article/pii/S2214426922000994 |
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