Abstract :

Hereditary Hemochromatosis (HH) is an autosomal recessive genetic disease characterized by abnormalities in iron regulation, mostly due to mutations in the HFE gene, leading to increased iron absorption due to hepcidin deficiency. The classification of HH is based on the type of mutated gene, which must be distinguished from non-genetic conditions that cause secondary elevations in serum iron levels such as multiple transfusions and increased iron supplementation. Pathophysiological mechanisms of HH include increased absorption of iron in the upper intestine, decreased expression of the iron regulatory hormone hepcidin, altered function of the HFE protein, and tissue damage and fibrogenesis caused by iron overload. The human body is physiologically unable to excrete excess iron load so excess iron in serum will be deposited in various organs, causing organ dysfunction. The clinical manifestations of hemochromatosis vary widely depending on the location of iron deposition in the organ. The classic clinical triad of hemochromatosis is liver cirrhosis, skin pigmentation, and diabetes mellitus. Hemochromatosis can be screened for and diagnosed by examining serum ferritin levels, transferrin saturation, unsaturated iron-binding capacity, total iron-binding capacity, liver biopsy, magnetic resonance imaging, and genetic testing. The main treatment for hemochromatosis at this time is phlebotomy although other therapeutic methods can also be used to help lower iron levels and improve the patient’s clinical course, such as therapy with chelating agents, erythrocytopharesis, and liver transplantation. If hemochromatosis is not treated, the patient can experience progressive liver damage leading to cirrhosis and hepatocellular carcinoma, and complications due to damage to various tissues and organs.

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Keywords :

Hereditary Hemochromatosis, HFE gene mutations, Iron Overload, Iron Regulation Abnormalities

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References :

1. Wallace, D. F., & Subramaniam, V. N. (2016). The global prevalence of HFE and non-HFE hemochromatosis estimated from analysis of next-generation sequencing data. Genetics in Medicine, 18(6), 618–626.

https://doi.org/10.1038/gim.2015.140

1. Kowdley, K. v., Brown, K. E., Ahn, J., & Sundaram, V. (2019). ACG Clinical Guideline: Hereditary Hemochromatosis. American Journal of Gastroenterology, 114(8), 1202–1218. https://doi.org/10.14309/ajg.0000000000000315
2. Brissot, P., & Brissot, E. (2020). What’s Important and New in Hemochromatosis?

4. Clinical Hematology International,       2(4),        https://doi.org/10.2991/chi.k.200726.001

1. Adel Aboulkhair, A., Almuataz Ezzi, A. I., Abdullah Alharbi, T., Sultan Alzughbi, A., Melih Marick Alshammari, Kh., Musallam Alshammari, S. and et al. (2020). Evaluation of  Hemochromatosis, Diagnosis and Management: Simple Literature Review. Arch Pharma Pract, 11(3):7101-3.
2. Brissot, P., Cavey, T., Ropert, M., Guggenbuhl, P., & Loreal, O. (2017). Clinical management of hemochromatosis: current perspectives. International Journal of Clinical Transfusion Medicine, Volume 5, 1–7. https://doi.org/10.2147/ijctm.s105214
3. Daniłowicz-Szymanowicz, L., Światcząk, M., Sikorska, K., Starzyński, R. R., Raczak, A., & Lipiński, P. (2021). Pathogenesis, diagnosis, and clinical implications of hereditary hemochromatosis—the cardiological point of view. In Diagnostics (Vol. 11, Issue 7). MDPI. https://doi.org/10.3390/diagnostics11071279
4. Fitzsimons, E. J., Cullis, J. O., Thomas, D. W., Tsochatzis, E., & Griffiths, W. J. H. (2018). Diagnosis and therapy of genetic haemochromatosis (review and 2017 update). In British Journal of Haematology (Vol. 181, Issue 3, pp. 293–303). Blackwell Publishing Ltd. https://doi.org/10.1111/bjh.15164
5. Kanwar, P., & Kowdley, K. v. (2013). Diagnosis and treatment of hereditary hemochromatosis: An update. In Expert Review of Gastroenterology and Hepatology (Vol. 7,                Issue 6, pp. 517–530). Expert Reviews Ltd.

https://doi.org/10.1586/17474124.2013.816114

1. Jl, P., &   Rawla P. (n.d.). Hemochromatosis. https://www.ncbi.nlm.nih.gov/books/NBK430862/#_NBK430862_pubdet_
2. Adams, P. C. (2020). An Official Learning Resource of AASLD. In 83 | CliniCal liver Disease (Vol. 16).
3. Zoller, H., & Knisely, A. S. (2012). Neonatal iron overload and tissue siderosis due to gestational alloimmune liver disease. Journal of Hepatology, 56(6), 1351–1355. https://doi.org/10.1016/j.jhep.2012.01.010
4. Muckenthaler, Martina U. (2014). How mutant HFE causes hereditary hemochromatosis (Vol. 124, Issue 8).
5. Rishi, G., Secondes, E. S., & Nathan Subramaniam, V. (2018). Hemochromatosis: Evaluation of the dietary iron model and regulation of hepcidin. Biochimica et Biophysica Acta – Molecular Basis of Disease, 1864(8), 2550–2556. https://doi.org/10.1016/j.bbadis.2018.05.005
6. Bacon R, Adams C. Diagnosis and Management of Hemochromatosis: 2011 Practice Guideline by the American Association for the Study of Liver Disease, Hepatology, 2011; 54: 328-341.
7. Janssen M, Swinkels D. Hereditary Haemochromatosis. Best Practice and Research Clinicl Gastroenterology, 2009; 171-183.
8. Pietrangelo A. Reviews in Basic and Clinical Gastroenterology ang Hepatology, Gastroenterology, 2010; 139: 393-408.
9. Powell L. Hereditary Hemochromatosis and Iron Overload Disease. Journal of Gastroenterology and Hepatology, 2002; 17: 191-195.
10. Adams, P. C., Barton, J. C., Guo, H., Alter, D., & Speechley, M. (2015). Serum ferritin is a biomarker for liver mortality in the Hemochromatosis and Iron Overload Screening Study (Vol. 14, Issue 3).
11. Saxena R. Special Stains in Interpretation of Liver Biopsies. Division of Transplantation Departement of Surgery Indiana University, USA. 2010: 92-98.
12. Torbenson M, Nalesnik M, Bourne R. Calculation and Interpretation of Heptic Iron Index. http://tpis.upmc.com. Accessed januari 2016.
13. Porter JL, Rawla P. Hemochromatosis. [Updated 2021 Dec 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430862/
14. Adams PC. Epidemiology and diagnostic testing for hemochromatosis and iron overload. Int J Lab Hematol. 2015 May;37 Suppl 1:25-30. doi: 10.1111/ijlh.12347.
15. Cancado, R. D., Alvarenga, A. M., & Santos, P. C. J. (2022). HFE hemochromatosis: an overview about therapeutic recommendations. Hematology, Transfusion and Cell Therapy, 44(1), 95–99. https://doi.org/10.1016/j.htct.2021.06.020
16. de Buck, E., Pauwels, N. S., Dieltjens, T., Compernolle, V., & Vandekerckhove, P. (2012). Is blood of uncomplicated hemochromatosis patients safe and effective for blood transfusion? A systematic review.