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Iron Overload

MedGen UID:
79398
•Concept ID:
C0282193
•
Disease or Syndrome
Synonym: Overload, Iron
SNOMED CT: Iron overload (60737008); Increased storage iron (60737008); Iron excess (60737008)

Definition

Accumulation of iron in the tissues. It may be a manifestation of an inherited disorder (e.g., hemochromatosis) or acquired (in patients with repeated blood transfusions). Symptoms include hepatomegaly, arthritis, diabetes mellitus, and bronzed skin. If untreated it has a progressive course and may lead to death. [from NCI]

Professional guidelines

PubMed

EASL Clinical Practice Guidelines on haemochromatosis.
European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; European Association for the Study of the Liver
J Hepatol 2022 Aug;77(2):479-502. Epub 2022 Jun 1 doi: 10.1016/j.jhep.2022.03.033. PMID: 35662478
Current status of beta-thalassemia and its treatment strategies.
Ali S, Mumtaz S, Shakir HA, Khan M, Tahir HM, Mumtaz S, Mughal TA, Hassan A, Kazmi SAR, Sadia, Irfan M, Khan MA
Mol Genet Genomic Med 2021 Dec;9(12):e1788. Epub 2021 Nov 5 doi: 10.1002/mgg3.1788. PMID: 34738740Free PMC Article
ACG Clinical Guideline: Hereditary Hemochromatosis.
Kowdley KV, Brown KE, Ahn J, Sundaram V
Am J Gastroenterol 2019 Aug;114(8):1202-1218. doi: 10.14309/ajg.0000000000000315. PMID: 31335359

Recent clinical studies

Etiology

The IRONy in Athletic Performance.
Kardasis W, Naquin ER, Garg R, Arun T, Gopianand JS, Karmakar E, Gnana-Prakasam JP
Nutrients 2023 Nov 28;15(23) doi: 10.3390/nu15234945. PMID: 38068803Free PMC Article
Iron chelation therapy.
Bruzzese A, Martino EA, Mendicino F, Lucia E, Olivito V, Bova C, Filippelli G, Capodanno I, Neri A, Morabito F, Gentile M, Vigna E
Eur J Haematol 2023 May;110(5):490-497. Epub 2023 Feb 8 doi: 10.1111/ejh.13935. PMID: 36708354
Iron overload modulates follicular microenvironment via ROS/HIF-1α/FSHR signaling.
Wu Y, Yang R, Lan J, Wu Y, Huang J, Fan Q, You Y, Lin H, Jiao X, Chen H, Cao C, Zhang Q
Free Radic Biol Med 2023 Feb 20;196:37-52. Epub 2023 Jan 10 doi: 10.1016/j.freeradbiomed.2022.12.105. PMID: 36638901
Iron and the Pathophysiology of Diabetes.
Harrison AV, Lorenzo FR, McClain DA
Annu Rev Physiol 2023 Feb 10;85:339-362. Epub 2022 Sep 22 doi: 10.1146/annurev-physiol-022522-102832. PMID: 36137277Free PMC Article
Alpha- and Beta-thalassemia: Rapid Evidence Review.
Baird DC, Batten SH, Sparks SK
Am Fam Physician 2022 Mar 1;105(3):272-280. PMID: 35289581

Diagnosis

Haemochromatosis.
Adams PC, Jeffrey G, Ryan J
Lancet 2023 May 27;401(10390):1811-1821. Epub 2023 Apr 27 doi: 10.1016/S0140-6736(23)00287-8. PMID: 37121243
Iron chelation therapy.
Bruzzese A, Martino EA, Mendicino F, Lucia E, Olivito V, Bova C, Filippelli G, Capodanno I, Neri A, Morabito F, Gentile M, Vigna E
Eur J Haematol 2023 May;110(5):490-497. Epub 2023 Feb 8 doi: 10.1111/ejh.13935. PMID: 36708354
Iron overload disorders.
Hsu CC, Senussi NH, Fertrin KY, Kowdley KV
Hepatol Commun 2022 Aug;6(8):1842-1854. Epub 2022 Jun 14 doi: 10.1002/hep4.2012. PMID: 35699322Free PMC Article
Alpha- and Beta-thalassemia: Rapid Evidence Review.
Baird DC, Batten SH, Sparks SK
Am Fam Physician 2022 Mar 1;105(3):272-280. PMID: 35289581
The Evaluation of Iron Deficiency and Iron Overload.
Gattermann N, Muckenthaler MU, Kulozik AE, Metzgeroth G, Hastka J
Dtsch Arztebl Int 2021 Dec 10;118(49):847-856. doi: 10.3238/arztebl.m2021.0290. PMID: 34755596Free PMC Article

Therapy

Emerging Therapies in β-Thalassemia.
Bou-Fakhredin R, Kuo KHM, Taher AT
Hematol Oncol Clin North Am 2023 Apr;37(2):449-462. doi: 10.1016/j.hoc.2022.12.010. PMID: 36907614
Iron chelation therapy.
Bruzzese A, Martino EA, Mendicino F, Lucia E, Olivito V, Bova C, Filippelli G, Capodanno I, Neri A, Morabito F, Gentile M, Vigna E
Eur J Haematol 2023 May;110(5):490-497. Epub 2023 Feb 8 doi: 10.1111/ejh.13935. PMID: 36708354
Long-term outcomes of lentiviral gene therapy for the β-hemoglobinopathies: the HGB-205 trial.
Magrin E, Semeraro M, Hebert N, Joseph L, Magnani A, Chalumeau A, Gabrion A, Roudaut C, Marouene J, Lefrere F, Diana JS, Denis A, Neven B, Funck-Brentano I, Negre O, Renolleau S, Brousse V, Kiger L, Touzot F, Poirot C, Bourget P, El Nemer W, Blanche S, Tréluyer JM, Asmal M, Walls C, Beuzard Y, Schmidt M, Hacein-Bey-Abina S, Asnafi V, Guichard I, Poirée M, Monpoux F, Touraine P, Brouzes C, de Montalembert M, Payen E, Six E, Ribeil JA, Miccio A, Bartolucci P, Leboulch P, Cavazzana M
Nat Med 2022 Jan;28(1):81-88. Epub 2022 Jan 24 doi: 10.1038/s41591-021-01650-w. PMID: 35075288
Management of pyruvate kinase deficiency in children and adults.
Grace RF, Barcellini W
Blood 2020 Sep 10;136(11):1241-1249. doi: 10.1182/blood.2019000945. PMID: 32702739
Milk thistle in liver diseases: past, present, future.
Abenavoli L, Capasso R, Milic N, Capasso F
Phytother Res 2010 Oct;24(10):1423-32. doi: 10.1002/ptr.3207. PMID: 20564545

Prognosis

Current status of beta-thalassemia and its treatment strategies.
Ali S, Mumtaz S, Shakir HA, Khan M, Tahir HM, Mumtaz S, Mughal TA, Hassan A, Kazmi SAR, Sadia, Irfan M, Khan MA
Mol Genet Genomic Med 2021 Dec;9(12):e1788. Epub 2021 Nov 5 doi: 10.1002/mgg3.1788. PMID: 34738740Free PMC Article
Changing patterns in the epidemiology of β-thalassemia.
Kattamis A, Forni GL, Aydinok Y, Viprakasit V
Eur J Haematol 2020 Dec;105(6):692-703. Epub 2020 Sep 21 doi: 10.1111/ejh.13512. PMID: 32886826Free PMC Article
Evolving therapies for lower-risk myelodysplastic syndromes.
Bewersdorf JP, Zeidan AM
Ann Hematol 2020 Apr;99(4):677-692. Epub 2020 Feb 20 doi: 10.1007/s00277-020-03963-1. PMID: 32078008
Cardiac involvement in hemochromatosis.
Gulati V, Harikrishnan P, Palaniswamy C, Aronow WS, Jain D, Frishman WH
Cardiol Rev 2014 Mar-Apr;22(2):56-68. doi: 10.1097/CRD.0b013e3182a67805. PMID: 24503941
Deferiprone: New insight.
Piga A, Roggero S, Vinciguerra T, Sacchetti L, Gallo V, Longo F
Ann N Y Acad Sci 2005;1054:169-74. doi: 10.1196/annals.1345.019. PMID: 16339662

Clinical prediction guides

Testing and Management of Iron Overload After Genetic Screening-Identified Hemochromatosis.
Savatt JM, Johns A, Schwartz MLB, McDonald WS, Salvati ZM, Oritz NM, Masnick M, Hatchell K, Hao J, Buchanan AH, Williams MS
JAMA Netw Open 2023 Oct 2;6(10):e2338995. doi: 10.1001/jamanetworkopen.2023.38995. PMID: 37870835Free PMC Article
Iron overload promotes intervertebral disc degeneration via inducing oxidative stress and ferroptosis in endplate chondrocytes.
Wang W, Jing X, Du T, Ren J, Liu X, Chen F, Shao Y, Sun S, Yang G, Cui X
Free Radic Biol Med 2022 Sep;190:234-246. Epub 2022 Aug 15 doi: 10.1016/j.freeradbiomed.2022.08.018. PMID: 35981695
Iron metabolism: pathophysiology and pharmacology.
Roemhild K, von Maltzahn F, Weiskirchen R, Knüchel R, von Stillfried S, Lammers T
Trends Pharmacol Sci 2021 Aug;42(8):640-656. Epub 2021 Jun 2 doi: 10.1016/j.tips.2021.05.001. PMID: 34090703Free PMC Article
Hereditary hemochromatosis: pathogenesis, diagnosis, and treatment.
Pietrangelo A
Gastroenterology 2010 Aug;139(2):393-408, 408.e1-2. Epub 2010 Jun 11 doi: 10.1053/j.gastro.2010.06.013. PMID: 20542038
Hereditary haemochromatosis.
Janssen MC, Swinkels DW
Best Pract Res Clin Gastroenterol 2009;23(2):171-83. doi: 10.1016/j.bpg.2009.02.004. PMID: 19414144

Recent systematic reviews

Calcium channel blockers for preventing cardiomyopathy due to iron overload in people with transfusion-dependent beta thalassaemia.
Padhani ZA, Gangwani MK, Sadaf A, Hasan B, Colan S, Alvi N, Das JK
Cochrane Database Syst Rev 2023 Nov 17;11(11):CD011626. doi: 10.1002/14651858.CD011626.pub3. PMID: 37975597Free PMC Article
Ferroptosis in acute kidney injury following crush syndrome: A novel target for treatment.
Qiao O, Wang X, Wang Y, Li N, Gong Y
J Adv Res 2023 Dec;54:211-222. Epub 2023 Jan 24 doi: 10.1016/j.jare.2023.01.016. PMID: 36702249Free PMC Article
Macrophage Subsets and Death Are Responsible for Atherosclerotic Plaque Formation.
Li H, Cao Z, Wang L, Liu C, Lin H, Tang Y, Yao P
Front Immunol 2022;13:843712. Epub 2022 Mar 30 doi: 10.3389/fimmu.2022.843712. PMID: 35432323Free PMC Article
Serum or plasma ferritin concentration as an index of iron deficiency and overload.
Garcia-Casal MN, Pasricha SR, Martinez RX, Lopez-Perez L, Peña-Rosas JP
Cochrane Database Syst Rev 2021 May 24;5(5):CD011817. doi: 10.1002/14651858.CD011817.pub2. PMID: 34028001Free PMC Article
Guidelines on the diagnosis and treatment of iron deficiency across indications: a systematic review.
Peyrin-Biroulet L, Williet N, Cacoub P
Am J Clin Nutr 2015 Dec;102(6):1585-94. Epub 2015 Nov 11 doi: 10.3945/ajcn.114.103366. PMID: 26561626

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