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Iron overload due to SLC40A1 mutation of type 4 hereditary hemochromatosis

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A Letter to the Editor to this article was published on 27 November 2023

Abstract

Hereditary hemochromatosis type 4 is an autosomal-dominant inherited disease characterized by a mutation in the SLC40A1 gene encoding ferroportin. This condition can be further subdivided into types 4A (loss-of-function mutations) and 4B (gain-of-function mutations). To date, only a few cases of type 4B cases have been reported, and the treatment has not been clearly mentioned. Here, we report a genotype of hereditary hemochromatosis type 4B involving the heterozygous mutation c.997 T > C (p. Tyr333His) in SLC40A1. The patient was treated with red blood cell apheresis every month for 1 year, followed by oral deferasirox, and the combined therapy was found to be effective.

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References

  1. An P, Jiang L, Guan Y, Wang H, Wang J, Tian Y, Yang W, Shi Y, Xue J, Min J, Wang F (2017) Identification of hereditary hemochromatosis pedigrees and a novel SLC40A1 mutation in Chinese population. Blood Cells Mol Dis 63:34–36. https://doi.org/10.1016/j.bcmd.2017.01.002

    Article  CAS  PubMed  Google Scholar 

  2. Wang Y, Du Y, Liu G, Guo S, Hou B, Jiang X, Han B, Chang Y, Nie G (2017) Identification of novel mutations in HFE, HFE2, TfR2, and SLC40A1 genes in Chinese patients affected by hereditary hemochromatosis. Int J Hematol 105(4):521–525. https://doi.org/10.1007/s12185-016-2150-8

    Article  CAS  PubMed  Google Scholar 

  3. Lyu TX, Zhang W, Li XJ, Xu AJ, Zhao XY, Ou XJ, Huang J (2016) Characteristics of gene mutation in Chinese patients with hereditary hemochromatosis. J Clin Hepatol 32(8):1571–1574. https://doi.org/10.3969/j.issn.1001-5256.2016.08.028

    Article  CAS  Google Scholar 

  4. Zhang W, Lv T, Huang J, Ou X (2017) Type 4B hereditary hemochromatosis associated with a novel mutation in the SLC40A1 gene: a case report and a review of the literature. Medicine (Baltimore) 96(38):e8064. https://doi.org/10.1097/md.0000000000008064

    Article  CAS  PubMed  Google Scholar 

  5. Zhang W, Xu A, Li Y, Zhao S, Zhou D, Wu L, Zhang B, Zhao X, Wang Y, Wang X, Duan W, Wang Q, Nan Y, You H, Jia J, Ou X, Huang J, China Registry of Genetic/Metabolic Liver Diseases G (2019) A novel SLC40A1 p. Y333H mutation with gain of function of ferroportin: a recurrent cause of haemochromatosis in China. Liver Int 39(6):1120–1127. https://doi.org/10.1111/liv.14013

    Article  CAS  PubMed  Google Scholar 

  6. Zhu CY, Chen Q, Feng ZX (2021) Hereditary hemochromatosis caused by mutation in the SLC40A1 gene: a case report. J Clin Hepatol 37(5):1180–1182. https://doi.org/10.3969/j.issn.1001-5256.2021.05.041

    Article  Google Scholar 

  7. Wu LY, Song ZY, Li QH, Mou LJ, Yu YY, Shen SS, Song XX (2021) Iron chelators reverse organ damage in type 4B hereditary hemochromatosis: case reports. Medicine (Baltimore) 100(13):e25258. https://doi.org/10.1097/md.0000000000025258

    Article  CAS  PubMed  Google Scholar 

  8. Nishina S, Tomiyama Y, Ikuta K, Tatsumi Y, Toki Y, Kato A, Kato K, Yoshioka N, Sasaki K, Hara Y, Hino K (2021) Long-term phlebotomy successfully alleviated hepatic iron accumulation in a ferroportin disease patient with a mutation in SLC40A1: a case report. BMC Gastroenterol 21(1):111. https://doi.org/10.1186/s12876-021-01674-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hankins JS, McCarville MB, Loeffler RB, Smeltzer MP, Onciu M, Hoffer FA, Li CS, Wang WC, Ware RE, Hillenbrand CM (2009) R2* magnetic resonance imaging of the liver in patients with iron overload. Blood 113(20):4853–4855. https://doi.org/10.1182/blood-2008-12-191643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hoffbrand AV, Taher A, Cappellini MD (2012) How I treat transfusional iron overload. Blood 120(18):3657–3669. https://doi.org/10.1182/blood-2012-05-370098

    Article  CAS  PubMed  Google Scholar 

  11. Le Tertre M, Ka C, Guellec J, Gourlaouen I, Ferec C, Callebaut I, Le Gac G (2017) Deciphering the molecular basis of ferroportin resistance to hepcidin: Structure/function analysis of rare SLC40A1 missense mutations found in suspected hemochromatosis type 4 patients. Transfus Clin Biol 24(4):462–467. https://doi.org/10.1016/j.tracli.2017.07.002

    Article  PubMed  Google Scholar 

  12. Qiao B, Sugianto P, Fung E, Del-Castillo-Rueda A, Moran-Jimenez MJ, Ganz T, Nemeth E (2012) Hepcidin-induced endocytosis of ferroportin is dependent on ferroportin ubiquitination. Cell Metab 15(6):918–924. https://doi.org/10.1016/j.cmet.2012.03.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Majore S, Bonaccorsi di Patti MC, Valiante M, Polticelli F, Cortese A, Di Bartolomeo S, De Bernardo C, De Muro M, Faienza F, Radio FC, Grammatico P, Musci G (2018) Characterization of three novel pathogenic SLC40A1 mutations and genotype/phenotype correlations in 7 Italian families with type 4 hereditary hemochromatosis. Biochim Biophys Acta Mol Basis Dis 1864(2):464–470. https://doi.org/10.1016/j.bbadis.2017.11.006

    Article  CAS  PubMed  Google Scholar 

  14. Sabelli M, Montosi G, Garuti C, Caleffi A, Oliveto S, Biffo S, Pietrangelo A (2017) Human macrophage ferroportin biology and the basis for the ferroportin disease. Hepatology 65(5):1512–1525. https://doi.org/10.1002/hep.29007

    Article  CAS  PubMed  Google Scholar 

  15. Pietrangelo A (2017) Ferroportin disease: pathogenesis, diagnosis and treatment. Haematologica 102(12):1972–1984. https://doi.org/10.3324/haematol.2017.170720

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Pietrangelo A (2010) Hereditary hemochromatosis: pathogenesis, diagnosis, and treatment. Gastroenterology 139(2):393–408. https://doi.org/10.1053/j.gastro.2010.06.013

    Article  PubMed  Google Scholar 

  17. Altamura S, Kessler R, Grone HJ, Gretz N, Hentze MW, Galy B, Muckenthaler MU (2014) Resistance of ferroportin to hepcidin binding causes exocrine pancreatic failure and fatal iron overload. Cell Metab 20(2):359–367. https://doi.org/10.1016/j.cmet.2014.07.007

    Article  CAS  PubMed  Google Scholar 

  18. Mayr R, Janecke AR, Schranz M, Griffiths WJ, Vogel W, Pietrangelo A, Zoller H (2010) Ferroportin disease: a systematic meta-analysis of clinical and molecular findings. J Hepatol 53(5):941–949. https://doi.org/10.1016/j.jhep.2010.05.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Billesbolle CB, Azumaya CM, Kretsch RC, Powers AS, Gonen S, Schneider S, Arvedson T, Dror RO, Cheng Y, Manglik A (2020) Structure of hepcidin-bound ferroportin reveals iron homeostatic mechanisms. Nature 586(7831):807–811. https://doi.org/10.1038/s41586-020-2668-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Preza GC, Ruchala P, Pinon R, Ramos E, Qiao B, Peralta MA, Sharma S, Waring A, Ganz T, Nemeth E (2011) Minihepcidins are rationally designed small peptides that mimic hepcidin activity in mice and may be useful for the treatment of iron overload. J Clin Invest 121(12):4880–4888. https://doi.org/10.1172/JCI57693

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Lescano MA, Tavares LC, Santos P (2017) Juvenile hemochromatosis: HAMP mutation and severe iron overload treated with phlebotomies and deferasirox. World J Clin Cases 5(10):381–383. https://doi.org/10.12998/wjcc.v5.i10.381

    Article  PubMed  PubMed Central  Google Scholar 

  22. Han Y, Zhang X (2019) Genetic diagnosis of hereditary hemochromatosis. J Clin Hepatol 35(8):1673–1679

    CAS  Google Scholar 

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Funding

This study was supported by Grant 2022YFA1103301 of National Key R&D Program of China and Grant 81890992 of National Natural Science Foundation of China.

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Authors and Affiliations

  1. State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, China

    Jing Hu, Yuan Li, Li Zhang, Guangxin Peng, Fengkui Zhang & Xin Zhao

  2. Tianjin Institutes of Health Science, Tianjin, 301600, China

    Jing Hu, Yuan Li, Li Zhang, Guangxin Peng, Fengkui Zhang & Xin Zhao

Authors
  1. Jing Hu
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  2. Yuan Li
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  3. Li Zhang
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  4. Guangxin Peng
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  5. Fengkui Zhang
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  6. Xin Zhao
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Contributions

JH investigated the pedigree and drafted manuscript; YL interpreted the imaging findings; LF and FZ served as the patient’s physicians; GP analyzed the sequencing data; XZ wrote and revised the manuscript, interpreted the data; all authors issued final approval for the version to be submitted.

Corresponding author

Correspondence to Xin Zhao.

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The authors declare no conflicts of interest.

Ethical approval

This study was approved by the Ethical Committee of the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College.

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Informed consent was obtained from the patient following the Declaration of Helsinki.

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Hu, J., Li, Y., Zhang, L. et al. Iron overload due to SLC40A1 mutation of type 4 hereditary hemochromatosis. Med Mol Morphol 56, 233–238 (2023). https://doi.org/10.1007/s00795-023-00359-8

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  • DOI: https://doi.org/10.1007/s00795-023-00359-8

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