Search

Background Iron is essential for hemoglobin synthesis during terminal erythropoiesis. To supply adequate iron the carrier transferrin is required together with transferrin receptor endosomal cycle and normal mitochondrial iron utilization. Iron and iron protein deficiencies result in different types of anemia. Iron-deficiency anemia is the commonest anemia worldwide due to increased requirements, malnutrition, chronic blood losses and malabsorption. Mutations of transferrin, transferrin receptor cycle proteins, enzymes of the first step of heme synthesis and iron sulfur cluster biogenesis lead to rare anemias, usually accompanied by iron overload. Hepcidin plays an indirect role in erythropoiesis by controlling plasma iron. Inappropriately high hepcidin levels characterize the rare genetic iron-refractory iron-deficiency anemia (IRIDA) and the common anemia of chronic disease. Iron modulates both effective and ineffective erythropoiesis: iron restriction reduces heme and alpha-globin synthesis that may be of benefit in thalassemia. Material and Methods This review relies on the analysis of the most recent literature and personal data. Results Erythropoiesis controls iron homeostasis, by releasing erythroferrone that inhibits hepcidin transcription to increase iron acquisition in iron deficiency, hypoxia and EPO treatment. Erythroferrone, produced by EPO-stimulated erythropoiesis, inhibits hepcidin only when the activity of BMP/SMAD pathway is low, suggesting that EPO somehow modulates the latter signaling. Erythroblasts sense circulating iron through the second transferrin receptor (TFR2) that, in animal models, modulates the sensitivity of the erythroid cells to EPO. Discussion The advanced knowledge of the regulation of systemic iron homeostasis and erythropoiesis-mediated hepcidin regulation is leading to the development of targeted therapies for anemias and iron disorders. [ABSTRACT FROM AUTHOR]

Hereditary hyperferritinaemia–cataract syndrome is an autosomal dominant disorder characterized by a constitutively increased synthesis of l-ferritin in the absence of iron overload. The disorder is associated with point mutations in the iron-responsive element (IRE) of l-ferritin mRNA. We report a new mutation, G51C, identified in two members of a Canadian family, presenting a moderate increase in serum ferritin and a clinically silent bilateral cataract. Gel retardation assays showed that the binding of the mutated IRE to iron-regulatory proteins (IRPs) was reduced compared with the wild type. Structural modelling predicted that the G51C induces a rearrangement of base pairing at the lateral bulge of the IRE structure which is likely to modify IRE conformation. [ABSTRACT FROM AUTHOR]

This is an observational retrospective study showing that hepcidin-25 and ferritin light chain are increased in malignant breast cancer and benign breast lesions compared with control individuals. A significant association between HER2 status and increased hepcidin-25 was also observed. Thus, assessment of plasma hepcidin-25 and iron-related parameters may improve breast cancer detection.Background Currently used CA15–3 and CEA have found their clinical application particularly in the follow-up of patients with advanced disease. Novel biomarkers are urgent, especially for improving early diagnosis as well as for discriminating between benign and malignant disease. Patients and methods In the present study, we used a proteomic approach based on surface-enhanced laser desorption/ionization–time of flight–mass spectrometry screening with the aim of identifying differentially expressed 2–30 kDa proteins in plasma of patients with malignant (65 cases) and benign (88 cases) breast lesions with respect to 121 healthy controls. Results We found that the most promising SELDI peaks were those corresponding to hepcidin-25 and ferritin light chain. We evaluated the capability of these peaks in predicting malignant and benign breast lesions using the area under the receiver operating characteristic curve (AUC). The results showed a good capacity to predict malignant breast lesions for hepcidin-25 [AUC: 0.82; 95% confidence interval (CI) 0.75–0.90] and ferritin light chain (AUC: 0.86; 95% CI 0.79–0.92). Conversely, a weak and satisfactory capability to predict benign breast lesion was observed for hepcidin-25 (AUC: 0.63; 95% CI 0.41–0.85) and ferritin light chain (AUC: 0.73; 95% CI 0.49–0.97). A significant association between HER2 status and hepcidin-25 was observed and the distribution of transferrin and ferritin were found significantly different in patients with breast cancer when compared with that of controls. Conclusions This study provides evidence that hepcidin and ferritin light chain level in plasma may be of clinical usefulness to predict malignant and benign disease with respect to healthy controls. [ABSTRACT FROM AUTHOR]

Unlabelled: Juvenile or type2 hemochromatosis is a rare autosomal recessive disorder which leads to severe iron overload early in life. As in the classic adult form of the disease iron toxicity causes liver cirrhosis, cardiomyopathy, and endocrine complications, but the onset of the disease is anticipated in the second to third decades of life. Experience of this disease in children is limited. Molecular diagnosis is unfeasible because the type2 hemochromatosis gene is still unknown, although it is known that the disease locus maps to chromosome 1q. Combining linkage analysis with markers encompassing chromosome 1 locus and a non-invasive method for liver iron quantitation we diagnosed juvenile hemochromatosis in a presymptomatic stage in an 11-year-old Italian child. A regular phlebotomy protocol reduced iron overload preventing all the disease complications.Conclusion: Juvenile hemochromatosis patients have severe iron overload within the first years of life, strengthening the greater iron absorption that occurs in this as compared to other types of hemochromatosis. Early detection is essential, because treatment in presymptomatic stages prevents organ damage. [ABSTRACT FROM AUTHOR]

Abstract: Hemojuvelin (HJV) is a recently discovered gene responsible for 1q-linked juvenile hemochromatosis. The majority of mutations characterized in this gene are rare and private, except G320V, identified in patients from different countries. Here, we report the clinical features and the molecular study of a young Irish patient presenting with severe cardiac disease related to iron overload. We sequenced the coding region and the exon–intron boundaries of genes associated with juvenile hemochromatosis, HAMP and HJV encoding hepcidin and hemojuvelin respectively. Two heterozygous HJV mutations were identified: the G320V mutation and the new Q116X mutation that cause a premature stop codon in the protein. This finding increases the number of mutations identified in HJV gene and underlines that the G320V is a recurrent mutation, even in Northern Europe. [Copyright &y& Elsevier]

Examines the juvenile hemochromatosis (JH) locus maps on chromosome 1q of patients with inborn error of iron metabolism. Use of genomewide search to map the JH locus on the long arm of chromosome 1; Influence of homozygosity mapping on the limitation of the region between markers D1S442 and D1S2347; Association of JH locus on the localization of chromosome in iron metabolism.