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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In mammalian cells, cellular iron homeostasis is maintained by the co-ordinated regulation of transferrin receptor and ferritin synthesis that occurs at the translational level. This regulation is mediated by iron-responsive elements (IREs) that are found within the untranslated regions (UTRs) of mRNA and by cytoplasmic mRNA-binding proteins, known as iron regulatory proteins (IRPs). When cellular iron is scarce, IRPs are available for binding the 5' IRE of ferritin mRNA, initiation of translation is prevented and ferritin synthesis is inhibited. By contrast, the presence of abundant intracellular iron prevents binding of the IRPs to the 5' IRE and allows efficient mRNA translation to proceed. Hereditary hyperferritinaemia/cataract syndrome (HHCS) arises as a result of various point mutations or deletions within a protein binding sequence in the 5'-UTR of the L-ferritin mRNA, which results in increased efficiency of L-ferritin translation. Each unique mutation confers a characteristic degree of hyperferritinaemia and severity of cataract in affected individuals. This exemplifies a new paradigm in which mutations in mRNA cis-acting elements may be responsible for phenotypic variability in disease states.
Best Pract Res Clin Haematol 2002 Jun
PMID:Hereditary hyperferritinaemia/ cataract syndrome. 1240 13

Iron and erythropoiesis are inextricably linked. Erythropoiesis is a dynamic process that requires 30-40 mg of iron per day. In normal circumstances this is met from red cell destruction but in anaemia this will not be the case. Reduced iron stores will limit iron supply to erythroblasts but normal or raised iron stores may not be able to supply iron fast enough. This is particularly true when the marrow is stimulated by erythropoietin therapy; the most common cause of failure to respond is "functional iron deficiency"'. This entity can only be effectively addressed by intravenous iron therapy. While haemoglobin and serum ferritin concentrations reflect the major iron pools, iron supply to erythroid cells can only be assessed by measuring effective haemoglobinization through the percentage of hypochromic red cells in the circulation.
Best Pract Res Clin Haematol 2002 Jun
PMID:Erythropoiesis and iron. 1240 14

We present the results on Anaemia Management in Fresenius Medical Care Spain dialysis centres as reported by EuCliD (European Clinical Database), evaluating a population of 4,426 patients treated in Spain during the year 2001. To analyse the erythropoietin dose and the haemoglobin levels we divided the population in two groups according to the time with dialysis treatment: patients treated less than six months and patients between six months, and four years on therapy. We compared our results with the evidence based recommendations Guidelines: the European Best Practice Guidelines (EBPG) and the US National Kidney Foundation (NKF-K/DOQI). We also compared our results with those presented by the ESAM2 on 2,618 patients on dialysis in Spain carried out in the second half of the year 2000. We observed that 70% of the population reaches an haemoglobin value higher that 11 g/dl, with a mean erythropoietin (rHu-EPO) dose of 111.9 Ul/kg weight/week (n = 3,700; SD 74.9). However, for those patients on treatment for less than six months, the mean Haemoglobin only reaches 10.65 g/dl (n = 222; SD 1.4). The rHu-EPO was administrated subcutaneously in 70.2% of the patients. About the iron therapy, 86% of the patients received iron treatment and the administration route was intravenous in 93% of the population. The ferritin levels were below 100 micrograms/dl in 10% of the patients and 26.4% showed a transferrin saturation index (TSAT) below 20%. The erythropoieting resistance index (ERI), as rHu-EPO/haemoglobin, has been used to evaluate the response to rHu-Epo, according to different variables. It was observed that the following factors lead to a higher rHu-EPO resistance: intravenous rHu-EPO as administration route, the presence of hypoalbuminemia, increase of protein C reactive, Transferrin saturation below 20% and starting dialysis during the last six months.
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PMID:[Anemia management in haemodialysis. EuCliD database in Spain]. 1251 89

A large body of evidence indicates that the level of serum ferritin parallels the concentration of storage iron within the body, regardless of the cell type in which it is stored. Elevated serum ferritin levels, in the absence of inflammation and liver disease, are currently taken to indicate increased iron stores and require further investigation to determine the site of iron overload. Until recently, the only genetic disorder with elevated serum ferritin levels known in Western countries was hereditary HLA-related HFE-related genetic haemochromatosis in Caucasians (HFE, OMIM 235200), and a high serum ferritin in apparently healthy persons was considered suggestive of this disease. In the last few years, at least two novel genetic disorders of iron metabolism presenting as unexplained hyperferritinaemia have been recognized. The first one is hereditary hyperferritinaemia/cataract syndrome (HHCS, OMIM 600886). HHCS arises from various point mutations or deletions within a protein binding sequence in the 5'-UTR of the L-ferritin mRNA that results in increased efficiency of L-ferritin translation. The second one is haemochromatosis type 4, or HFE4 (OMIM 606069), or ferroportin disease. In this latter condition, reticuloendothelial iron overload and hyperferritinaemia are caused by loss-of-function mutations in the SLC11A3 gene that mainly impair macrophage iron recycling. These genetic disorders should be taken into account in the differential diagnosis of unexplained hyperferritinaemia.
Best Pract Res Clin Haematol 2005 Jun
PMID:Role of ferritin and ferroportin genes in unexplained hyperferritinaemia. 1573 88

Neuroferritinopathy is a dominantly inherited movement disorder characterized by deposition of iron and ferritin in the brain, normal or low serum ferritin levels, and highly variable clinical features. The disease, also named dominant adult-onset basal ganglia disease, is associated with a nucleotide insertion that modifies the last 22 amino acids of the ferritin L-chain. A similar dominant movement disorder in a French family was associated with a nucleotide insertion that modifies the last nine amino acids of the same molecule. Both disorders show ferritin and iron precipitates in the basal ganglia of the brain. Here we present the structural aspects of the two mutations, as well studies on cellular models aimed at understanding the molecular basis of the disorder. The results indicate that the mutations affect protein folding and stability, and that the expression of one of the two variant ferritins increases intracellular iron availability and sensitivity to oxidative damage.
Best Pract Res Clin Haematol 2005 Jun
PMID:Neuroferritinopathy: a neurodegenerative disorder associated with L-ferritin mutation. 1573 89

Anaemia is typically the first clue to iron deficiency, but an isolated haemoglobin measurement has both low specificity and low sensitivity. The latter can be improved by including measures of iron-deficient erythropoiesis such as the transferrin iron saturation, mean corpuscular haemoglobin concentration, erythrocyte zinc protoporphyrin, percentage of hypochromic erythrocytes or reticulocyte haemoglobin concentration. However, the changes in these measurements with iron deficiency are indistinguishable from those seen in patients with the anaemia of chronic disease. The optimal diagnostic approach is to measure the serum ferritin as an index of iron stores and the serum transferrin receptor as a index of tissue iron deficiency. The treatment of iron deficiency should always be initiated with oral iron. When this fails because of large blood losses, iron malabsorption, or intolerance to oral iron, parenteral iron can be given using iron dextran, iron gluconate or iron sucrose.
Best Pract Res Clin Haematol 2005 Jun
PMID:Diagnosis and management of iron-deficiency anaemia. 1573 93

When erythropoietin (epoetins or darbepoetin) is used to treat the anemias of chronic renal failure, cancer chemotherapy, inflammatory bowel diseases, HIV infection and rheumatoid arthritis, functional iron deficiency rapidly ensues unless individuals are iron-overloaded from prior transfusions. Therefore, iron therapy is essential when using erythropoietin to maximize erythropoiesis by avoiding absolute and functional iron deficiency. Body iron stores (800-1200 mg) are best maintained by providing this much iron intravenously in a year, or more if blood loss is significant (in hemodialysis patients this can be 1-3 g). There is no ideal method for monitoring iron therapy, but serum ferritin and transferrin iron saturation are the most common tests. Iron deficiency is also detected by measuring the percentage of hypochromic red blood cells, content of hemoglobin in reticulocytes, soluble transferrin receptor levels, and free erythrocyte protoporphyrin values, but iron overload is not monitored by these tests. Iron gluconate and iron sucrose are the safest intravenous medications.
Best Pract Res Clin Haematol 2005 Jun
PMID:Iron requirements in erythropoietin therapy. 1573 95

Hypoparathyroidism is thought to be a rare consequence of iron overload seen in beta-thalassemic transfused patients. This study was conducted to determine the prevalence of hypoparathyroidism in a large number of beta-thalassemic patients, and its potential correlation with the presence of other endocrinopathies caused by iron overload. Serum and urine biochemical parameters were measured in 243 thalassemic patients (136 females and 107 males) in order to determine the prevalence of hypoparathyroidism and evaluate bone turnover. The patients were divided into two groups according to the presence of hypoparathyroidism. We compared the prevalence of other endocrinopathies and disease complications in the two groups. Hypoparathyroidism was detected in 13.5% of the patients (33 subjects; 17 males and 16 females). Serum-intact parathyroid hormone, and total and ionized calcium were significantly lower, while phosphorus was significantly higher in thalassemic patients with hypoparathyroidism. The reduction in BMD was more prominent in normal thalassemic patients (Z score = -2.246 +/- 0.97) compared with those with hypoparathyroidism (Z score = -1.975 +/- 0.89), although the difference was not statistically significant. Disturbed glucose metabolism was more common in patients with hypoparathyroidism (P < 0.05). In addition, heart dysfunction was statistically more frequent in this group (odds ratio = 2.51, P < 0.05). Hypoparathyroidism is a not infrequently observed complication in thalassemic patients. Since the concentration of ferritin is not a valuable tool in the prediction of the development of hypoparathyroidism, parathyroid function should be tested periodically, particularly when other iron overload-associated complications occur.
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PMID:Hypoparathyroidism in transfusion-dependent patients with beta-thalassemia. 1650 21

The Optimal Renal Anaemia Management Assessment trial prospectively examined the impact of implementing European Best Practice Guidelines on outcomes in the management of renal anemia. Baseline data give an insight to standards of clinical care and provide a basis for a future comparison of guideline target attainment with final results. Fifty-three centers from eight European countries enrolled 739 patients with stage II-V chronic kidney disease who were either anemic (hemoglobin <11 g/dL) or treated with erythropoiesis-stimulating agents and/or iron supplementation. Patients were followed over 6-8 months in centers that were randomly allocated to either group A or B (i.e., with or without a computerized clinical decision support tool after baseline). The latter provided guideline-based recommendations to physicians based on patient anemia-related data. We report patient characteristics and hemoglobin values from baseline and the prestudy period, focusing on regional differences. In all, 81% of patients were dialysis-dependent. Baseline mean hemoglobin values in dialysis patients were significantly higher in Western (11.8 g/dL) vs. Eastern Europe (10.6 g/dL; p < 0.0001). Similar proportions of patients (approximately 50%) had mean hemoglobin 10-12 g/dL suggesting Eastern European patients are treated to lower Hb levels. The guideline ferritin target was achieved by 85% of dialysis and 52% of non-dialysis patients; 81% of dialysis and 78% of non-dialysis patients attained the transferrin saturation target. Most patients (96%) were receiving erythropoiesis-stimulating agents. Anemia management in patients with chronic kidney disease shows considerable regional differences across Europe, and target attainment remains suboptimal in many European nephrology centers after the revised 2004 guidelines.
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PMID:Renal anemia: comparing current Eastern and Western European management practice (ORAMA). 1835 Apr 46

Adult-onset Still disease (AOSD) is an uncommon inflammatory condition of unknown origin typically characterized by four main (cardinal) symptoms: spiking fever > or =39 degrees C, arthralgia or arthritis, skin rash and hyperleucocytosis (> or =10,000 cells/mm3) with neutrophils > or =80%. As many other manifestations are possible, diagnosis is potentially challenging. Determination of the total and glycosylated ferritin levels, although not pathognomonic, can help in diagnosis. The disease evolution of AOSD can be monocyclic, polycyclic or chronic. In chronic disease, joint involvement is often predominant and erosions are noted in one-third of patients. No prognostic factors have been identified to date. Therapeutic strategies are from observational data. Corticosteroids are usually the first-line treatment. With inadequate response to corticosteroids, methotrexate appears the best choice to control disease activity and allow for tapering of steroid use. For refractory disease, biological therapy with agents blocking interleukin-1 (anakinra) and then those blocking interleukin-6 (tocilizumab) seem the most promising.
Best Pract Res Clin Rheumatol 2008 Oct
PMID:Adult-onset Still disease. 1902 63


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