IRON ABSORPTION AND LOADING IN Β-Thalassæmia INTERMEDIA

Pippard, Martin J.; Callender, Sheila T.; Warner, G. T.; Weatherall, D. J.

doi:10.1016/s0140-6736(79)92175-5

Cited by 203 publications

(112 citation statements)

References 10 publications

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“…This is particularly evident in untransfused patients, 2,28 in whom hyperabsorption of dietary iron is the sole source of iron overload. Secondary iron overload, mainly through its cardiac toxicity, is the primary cause of mortality in patients affected with b-thalassemia syndromes.…”

Section: Discussionmentioning

confidence: 99%

Erythroferrone contributes to hepcidin suppression and iron overload in a mouse model of β-thalassemia

Kautz¹,

Jung²,

Du³

et al. 2015

Blood

265

262

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Inherited anemias with ineffective erythropoiesis, such as β-thalassemia, manifest inappropriately low hepcidin production and consequent excessive absorption of dietary iron, leading to iron overload. Erythroferrone (ERFE) is an erythroid regulator of hepcidin synthesis and iron homeostasis. Erfe expression was highly increased in the marrow and spleen of HbbTh3/+ mice (Th3/+), a mouse model of thalassemia intermedia. Ablation of Erfe in Th3/+ mice restored normal levels of circulating hepcidin at 6 weeks of age, suggesting ERFE could be a factor suppressing hepcidin production in β-thalassemia. We examined the expression of Erfe and the consequences of its ablation in thalassemic mice from 3 to 12 weeks of age. The loss of ERFE in thalassemic mice led to full restoration of hepcidin mRNA expression at 3 and 6 weeks of age, and significant reduction in liver and spleen iron content at 6 and 12 weeks of age. Ablation of Erfe slightly ameliorated ineffective erythropoiesis, as indicated by reduced spleen index, red cell distribution width, and mean corpuscular volume, but did not improve the anemia. Thus, ERFE mediates hepcidin suppression and contributes to iron overload in a mouse model of β-thalassemia.

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Section: Discussionmentioning

confidence: 99%

Erythroferrone contributes to hepcidin suppression and iron overload in a mouse model of β-thalassemia

Kautz¹,

Jung²,

Du³

et al. 2015

Blood

265

262

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“…Progressive deposition of iron leads to dysfunction and failure of the major organs including heart, liver and endocrine glands such as pituitary, thyroid, parathyroid, adrenal and endocrine pancreas. Therefore, proper iron chelation therapy is mandatory for transfused patients with beta thalassemia major [3][4][5][6][7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Iron overload in beta thalassemia major patients

Karunaratna

Ranasingha

Mudiyanse

2017

Int J Blood Transfus Immunohematol

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Aims: Beta thalassemia is the most common monogenic hereditary hemoglobin disorder, which poses a major health burden to SriLanka. Regular transfusions of erythrocytes required for survival of these patients lead to inevitable iron overload, which is manifested, by elevated serum ferritin levels. Progressive deposition of iron leads to dysfunction and failure of the major organs. The aim of this study was to evaluate the iron overload of the beta thalassemia major patients in one of the thalassemia centres in Sri Lanka and to find its effect on growth status of the patients. Methods: The study included forty patients with confirmed diagnosis of beta thalassemia major, undergoing any chelation treatment. The mean age of the study group was 10.97±5.9 years with a range of 2-20 years. The patients were interviewed for the socio-demographic variables and their medical histories were obtained from the hospital files. Serum ferritin concentration, height and weight of the patients were measured and body mass index (BMI) was calculated. Results: The mean serum ferritin concentration was 2992.2±1575.35 ng/ml which showed a significant correlation with age and duration of blood transfusion. The mean z-score for height was -2.3±1.06 and 50% of the patients were stunted. The mean z-score for BMI was -1.32±1.28 and 35% of the patients were wasted. Both height and BMI had no significant correlation with iron overload of the patients. Conclusion: Iron overload and growth retardation were common in beta thalassemia major patients of the treatment center evaluated in this study in Sri Lanka. However, there was no significant relationship between physical growth and iron overload.

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“…Regular transfusions may double the rate of iron accumulation. In these patients, IE often worsens over time, exacerbating anemia, iron absorption, and splenomegaly (3). Increased gastrointestinal iron absorption may also play a role in transfused β-thalassemia major patients, increasing when hemoglobin (Hb) levels decrease (4).…”

mentioning

confidence: 99%

“…The iron absorbed by patients with β-thalassemia intermedia or th3/+ mice is excessive relative to the amount of iron needed to maintain a Hb of 9 g/dl (2,3,8). In this case, liver parenchymal cells store the surplus iron.…”

mentioning

confidence: 99%

Hepcidin as a therapeutic tool to limit iron overload and improve anemia in β-thalassemic mice

Gardenghi¹,

Ramos²,

Marongiu³

et al. 2010

J. Clin. Invest.

209

216

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Excessive iron absorption is one of the main features of β-thalassemia and can lead to severe morbidity and mortality. Serial analyses of β-thalassemic mice indicate that while hemoglobin levels decrease over time, the concentration of iron in the liver, spleen, and kidneys markedly increases. Iron overload is associated with low levels of hepcidin, a peptide that regulates iron metabolism by triggering degradation of ferroportin, an iron-transport protein localized on absorptive enterocytes as well as hepatocytes and macrophages. Patients with β-thalassemia also have low hepcidin levels. These observations led us to hypothesize that more iron is absorbed in β-thalassemia than is required for erythropoiesis and that increasing the concentration of hepcidin in the body of such patients might be therapeutic, limiting iron overload. Here we demonstrate that a moderate increase in expression of hepcidin in β-thalassemic mice limits iron overload, decreases formation of insoluble membrane-bound globins and reactive oxygen species, and improves anemia. Mice with increased hepcidin expression also demonstrated an increase in the lifespan of their red cells, reversal of ineffective erythropoiesis and splenomegaly, and an increase in total hemoglobin levels. These data led us to suggest that therapeutics that could increase hepcidin levels or act as hepcidin agonists might help treat the abnormal iron absorption in individuals with β-thalassemia and related disorders.

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IRON ABSORPTION AND LOADING IN Β-Thalassæmia INTERMEDIA

Cited by 203 publications

References 10 publications

Erythroferrone contributes to hepcidin suppression and iron overload in a mouse model of β-thalassemia

Erythroferrone contributes to hepcidin suppression and iron overload in a mouse model of β-thalassemia

Iron overload in beta thalassemia major patients

Hepcidin as a therapeutic tool to limit iron overload and improve anemia in β-thalassemic mice

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