Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three pediatric patients with refractory anemia with ringed sideroblasts (RARS) are presented. Bone marrow aspirates were examined using Romanowsky and Prussian blue iron stains in all three patients, and electron microscopic analysis was performed in one patient. All three patients had cytogenetic analysis of the bone marrow. Other studies included analysis of serum iron, total iron-binding capacity, ferritin, copper, vitamins B6 and B12, and folate levels. Antibody titers to Parvovirus, HIV, and other viruses were measured. The patients had contrasting clinical courses. Patients 1 and 2 had dysplastic hematopoietic features and cytogenetic findings (with either partial or one allele loss of chromosome 7), suggestive of myelodysplastic syndrome. Patient 1 experienced acute myeloid leukemia (AML) and had a good response to AML-directed therapy. Patient 2 had prolonged cytopenias and underwent bone marrow transplantation (BMT). Patient 3 had features suggestive of refractory anemia associated with mitochondrial cytopathy, including normal cytogenetics with pronounced vacuolization of marrow precursors. His anemia regressed spontaneously a few months after diagnosis. These patients represent two subgroups of pediatric RARS. Patients with the myelodysplastic syndrome (MDS) type may progress to cytopenias or leukemia and may require aggressive therapy; the type is characterized by clonal cytogenetic findings. The non-MDS type, which may relate to mitochondrial cytopathy, often shows spontaneous regression and requires only supportive treatment; it has normal cytogenetic findings.
 ...
PMID:Refractory anemia with ringed sideroblasts in children: two diseases with a similar phenotype? 1052 57

Effective management of early anaemia in the course of chronic renal insufficiency requires the following: (i) implementing an efficient diagnostic strategy to exclude common contributing factors; (ii) initiating epoetin therapy for the majority of patients; for and (iii) ensuring adequate iron supply erythropoiesis. Diagnostic inquiry is warranted whenever the haemoglobin concentration is below the normal range adjusted for age and gender. The most efficient diagnostic approach is to assume erythropoietin deficiency, exclude iron deficiency, and pursue further diagnostic tests only when red-cell indices are abnormal or when leukopenia or thrombocytopenia are also present. Macrocytosis should prompt an inquiry into alcoholism, B12 deficiency, or folate deficiency. Microcytosis suggests iron deficiency or thalassaemia. Associated cytopenias raise the possibility of alcohol toxicity, pernicious anaemia, malignancy, or myelodysplastic syndrome. Epoetin therapy is warranted whenever the haemoglobin concentration has fallen below 10.0 g/dl. To initiate therapy prior to dialysis, epoetin should be administered at an average dose of 100 IU/kg/week (80-120 IU/kg/week, 50-150 IU/kg/ week) by subcutaneous injection. Haemoglobin concentration should be monitored every 2 weeks and the epoetin dose adjusted by increments or decrements of 25% to maintain a rate of rise of haemoglobin concentration of 0.2-0.6 g/dl (0.3 0.6 g/dl/week, 0.2-0.5 g/dl/week). When the target range is achieved, the dose of epoetin should be continually adjusted to maintain a stable haemoglobin concentration. Transferrin saturation and ferritin concentration should be monitored monthly, and sufficient iron provided to maintain transferrin saturation above 20%. The lower the haemoglobin concentration, the greater the likelihood that future intravenous iron will be required. Oral iron supplements should be avoided, since they are costly, ineffective, and troublesome to patients. Finally, a blunted therapeutic response to epoetin therapy provides important diagnostic information and gnostic inquiry.
 ...
PMID:Management of early renal anaemia: diagnostic work-up, iron therapy, epoetin therapy. 1103 56

Anemia should not be accepted as an inevitable consequence of aging. A cause is found in approximately 80 percent of elderly patients. The most common causes of anemia in the elderly are chronic disease and iron deficiency. Vitamin B12 deficiency, folate deficiency, gastrointestinal bleeding and myelodysplastic syndrome are among other causes of anemia in the elderly. Serum ferritin is the most useful test to differentiate iron deficiency anemia from anemia of chronic disease. Not all cases of vitamin B12 deficiency can be identified by low serum levels. The serum methylmalonic acid level may be useful for diagnosis of vitamin B12 deficiency. Vitamin B12 deficiency is effectively treated with oral vitamin B12 supplementation. Folate deficiency is treated with 1 mg of folic acid daily.
 ...
PMID:Anemia in the elderly. 1103 74

Circulating serum transferrin receptor level was measured using mouse monoclonal antibody against transferrin receptor (Orion Diagnostica, Finland) in 126 patients with various disorders of erythropoiesis and the results were compared to those obtained form control group consisted of 30 healthy volunteers with normal iron stores. Serum transferrin receptor level was significantly elevated in patients with iron deficiency and in all patients with hyperplastic erythropoiesis (hereditary spherocytosis, immune hemolytic anemia, beta thalassemia, myelodysplasia). Measurement of circulating serum transferrin receptor level was a sensitive indicator of iron depletion as well as a helpful parameter in differential diagnosis between iron deficiency and anemia of chronic disease where circulating transferrin receptor level was not elevated. Index transferrin receptor/ferritin calculated as a ratio of circulating serum transferrin receptor level to log serum ferritin level was a more sensitive parameter than measurement of serum transferrin receptor not only for determination of patients with anemia of chronic disease, but also for discrimination of patients with elevated serum transferrin receptor level due to true iron deficiency from those with high serum transferrin receptor level caused by relative iron deficiency in hyperplastic erythropoiesis.
 ...
PMID:[Clinical importance of determining levels of circulating transferrin receptors in blood]. 1104 46

Transfusion of RBC units, the only current treatment for many myelodysplastic syndromes, and excess intestinal absorption of Fe related to dyserythopoiesis often result in iron overload. This condition is associated with high rates of morbidity and mortality. High-risk patients include those with refractory anemia, sideroblastic anemia, 5q-syndrome, patients with a good prognosis (low or lower intermediate international prognosis score), patients having received over 100 RBC units, and patients under the age of 70. Deferoxamine, while it can prevent iron overload, is a strenuous treatment requiring 8-to-12 hour-overnight subcutaneous injections. When patients comply with the regimen, it efficiently prevents mortality due to iron overload, but must be implemented early in the disorder, usually before transfusing 20 RBC concentrates. A simple way of monitoring iron overload is to measure seric ferritin levels and record the number of RBC concentrates. The chelating treatment should be modulated according to age, MDS type, international prognosis score, number of RBC units received, ferritin levels, and most of all, patient tolerance. The direct subcutaneous approach is currently being evaluated by the French Group for Myelodysplasias for its efficiency to prevent disorders, but seems to be both efficient and well complied with (a national protocol is under way). The recent findings on the proteins implied in iron recycling by macrophages after destruction of RBCs, may in the long term, enable us to manage patients with less burdensome treatments and more effective new oral chelates.
 ...
PMID:[Iron overload and myelodysplastic syndromes]. 1172 96

Serum soluble transferrin receptor (sTfR) has been reported to be higher in patients with iron deficiency or with elevated erythropoiesis. In the present study, serum sTfR was measured in various anemic diseases and their clinical significance was examined in a multi-institutional joint study. Serum sTfRs in patients with the following anemic diseases were markedly higher than those in normal healthy adults: non-treated iron deficiency anemia (IDA) (9.13 +/- 7.04 mg/l, n = 52, p < 0.0001), anemia of chronic disorders (ACD) (3.45 +/- 1.38 mg/l, n = 20, p < 0.0001), hemolytic anemia (HA) (5.57 +/- 3.26 mg/l, n = 17, p < 0.0001), and myelodysplastic syndrome (MDS) (4.03 +/- 2.83 mg/l, n = 20, p < 0.0001). There were significant differences between IDA and ACD (p < 0.0001), between aplastic anemia (AA) (1.58 +/- 1.26 mg/l, n = 16) and MDS (p < 0.001), and between AA and MDS with refractory anemia (MDS-RA) (4.16 +/- 3.40 mg/l, n = 9) (p < 0.02). In patients with chronic renal failure (CRF), serum sTfR levels and serum sTfR/log serum ferritin ratios (sTfR/F index) were compared in the two classified groups according to Muirhead's criteria, as IDA and non-IDA groups with or without recombinant human erythropoietin (rHuEPO) treatment. Significantly high levels of both serum sTfR (p < 0.0001) and the sTfR/F index (p < 0.0001) were observed in IDA without rHuEPO treatment. Especially in CRF with rHuEPO treatment, the sTfR/F index showed marked elevation in the IDA group (p < 0.0001) compared with serum sTfR (p < 0.001), indicating more diagnostic efficacy of the sTfR/F index for CRF with IDA. In conclusion, the serum sTfR concentration is a useful diagnostic tool for discrimination between IDA and ACD, and between AA and MDS-RA, and for the detection of iron deficiency in CRF patients in the Japanese population.
 ...
PMID:Diagnostic significance of serum soluble transferrin receptors in various anemic diseases: the first multi-institutional joint study in Japan. 1261 83

In the past seven years numerous genes that influence iron homeostasis have been discovered. Dr. Beutler provides a brief overview of these genes, genes that encode HFE, DMT-1, ferroportin, transferrin receptor 2, hephaestin, and hepcidin to lay the groundwork for a discussion of the various clinical forms of iron storage disease and how they differ from one another. In Section I, Dr. Beutler also discusses the types of hemochromatosis that exist as acquired and as hereditary forms. Acquired hemochromatosis occurs in patients with marrow failure, particularly when there is active ineffective erythropoiesis. Hereditary hemochromatosis is most commonly due to mutations in the HLA-linked HFE gene, and hemochromatosis clinically indistinguishable from HFE hemochromatosis is the consequence of mutations in three transferrin receptor-2 gene. A more severe, juvenile form of iron storage disease results from mutations of the gene encoding hepcidin or of a not-yet-identified gene on chromosome 1q. Autosomal dominant iron storage disease is a consequence of ferroportin mutations, and a polymorphism in the ferroportin gene appears to be involved in the African iron overload syndrome. Evidence regarding the biochemical and clinical penetrance of hemochromatosis due to mutations of the HFE gene is rapidly accumulating. These studies, emanating from several centers in Europe and the United States, all agree that the penetrance of hemochromatosis is much lower than had previously been thought. Probably only 1% of homozygotes develop clinical findings. The implications of these new findings for the management of hemochromatosis will be discussed. In Section II, Dr. Victor Hoffbrand discusses the management of iron storage disease by chelation therapy, treatment that is usually reserved for patients with secondary hemochromatosis such as occurs in the thalassemias and in patients with transfusion requirements due to myelodysplasia and other marrow failure states. Tissue iron can be estimated by determining serum ferritin levels, measuring liver iron, and by measuring cardiac iron using the MRI-T2* technique. The standard form of chelation therapy is the slow intravenous or subcutaneous infusion of desferoxamine. An orally active bidentate iron chelator, deferiprone, is now licensed in 25 countries for treatment of patients with thalassemia major. Possibly because of the ability of this compound to cross membranes, it appears to have superior cardioprotective properties. Agranulocytosis is the most serious complication of deferiprone therapy and occurs in about 1% of treated patients. Deferiprone and desferoxamine can be given together or on alternating schedules. A new orally active chelating agent ICL 670 seems promising in early clinical studies. In Section III, Dr. James Cook discusses the most common disorder of iron homeostasis, iron deficiency. He will compare some of the standard methods for identifying iron deficiency, the hemoglobin level, transferrin saturation, and mean corpuscular hemoglobin and compare these with some of the newer methods that have been introduced, specifically the percentage of hypochromic erythrocytes and reticulocyte hemoglobin content. The measurement of storage iron is achieved by measuring serum ferritin levels. The soluble transferrin receptor is a truncated form of the cellular transferrin receptor and the possible value of this measurement in the diagnosis of iron deficiency will be discussed. Until recently iron dextran was the only parental iron preparation available in the US. Sodium ferric gluconate, which has been used extensively in Europe for many years, is now available in the United States. It seems to have a distinct advantage over iron dextran in that anaphylactic reactions are much less common with the latter preparation.
 ...
PMID:Iron deficiency and overload. 1463 76

Anaemia is a common medical problem in elderly patients and is associated with an increased mortality and morbidity risk and a reduced quality of life. It is not known at which exact haemoglobin level investigations should be initiated in order to optimize the diagnostic efficacy. Serum ferritin determination remains the most accurate laboratory test for the diagnosis of iron deficiency anaemia and its differential diagnosis with the anaemia of chronic disease. The introduction of the metabolites methylmalonic acid and homocysteine has made it possible to diagnose vitamin B(12) and folate deficiencies at an early subclinical stage, even without neurological and haematological symptoms, but the clinical importance of this 'biochemical' diagnosis is unclear. Other causes of anaemia, such as myelodysplastic syndromes and chronic renal insufficiency, will become more and more common in the elderly because of the ageing of the population. Although erythropoietin analysis has no clear diagnostic value at the moment, it has become more and more obvious that its therapeutic importance in elderly patients with chronic anaemia is increasing. A substantial number of patients have an unexplained anaemia. Whether this is disease related, or may be attributed to an age-related anaemia, is still a matter of debate, but it is advisable to perform an extensive laboratory, cytogenetic, and morphological investigation before one should assess the anaemia as unexplained.
 ...
PMID:Strategies for the laboratory diagnosis of some common causes of anaemia in elderly patients. 1496 71

A novel ferritin type specifically targeted to mitochondria has been recently found in human and mouse. It is structurally and functionally similar to the cytosolic ferritins, well-characterized molecules found in most living systems which are designed to store and detoxify cellular iron. Cytosolic ferritins in mammals are ubiquitous while mitochondrial ferritin expression is restricted mainly to the testis, neuronal cells and islets of Langherans. In addition, it is abundant in the iron-loaded mitochondria of erythroblasts of patients with sideroblastic anaemia. The characterization of recombinant and transfected mitochondrial ferritin indicated that this protein has a role in protecting mitochondria from iron-induced damage. These data suggest that it is an interesting tool to study the iron metabolism in this organelle. In addition, it may be useful for the diagnosis of myelodysplastic syndromes and in protecting mitochondria from the toxic effects of excess iron.
 ...
PMID:Mitochondrial ferritin. 1520 3

Erythroid dysplasia is the pathologic hallmark of myelodysplastic syndromes (MDS). To develop a quantitative flow-cytometry approach to its evaluation, we analyzed the expression of CD71, CD105, cytosolic H-ferritin (HF), cytosolic L-ferritin (LF) and mitochondrial ferritin (MtF) in erythroblasts from 104 MDS patients, 69 pathologic control patients and 19 healthy subjects. Six-parameter, 4-color flow cytometry was employed, and data were expressed as mean fluorescence intensity. Compared with pathologic and healthy controls, MDS patients had higher expression of HF (P < 0.001) and CD105 (P < 0.001), and lower expression of CD71 (P < 0.001). MtF was specifically detected in MDS with ringed sideroblasts, and there was a close relationship between its expression and Prussian blue staining (r = 0.89, P < 0.001). In vitro cultures of myelodysplastic hematopoietic progenitors showed that both HF and MtF were expressed at a very early stage of erythroid differentiation, and that MtF expression is specifically related to mitochondrial iron loading. A classification function based on expression levels of HF, CD71 and CD105 allowed us to correctly classify > 95% of MDS patients. This flow-cytometry approach provides an accurate quantitative evaluation of erythroid dysplasia and allows a reliable diagnosis of sideroblastic anemia, and may therefore be a useful tool in the work-up of patients with MDS.
 ...
PMID:Flow cytometry evaluation of erythroid dysplasia in patients with myelodysplastic syndrome. 1649 94


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>