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)

In the majority of cases, microcytosis is the result of impaired hemoglobin synthesis. Disorders of iron metabolism and protoporphyrin and heme synthesis, as well as impaired globin synthesis, lead to defective hemoglobin production and to the generation of microcytosis and microcytic anemia. Iron deficiency anemie, anemia of chronic diseases, thalassemias, congenital sideroblastic anemias and homozygous HbE disease are the main representatives of microcytosis and microcytic anemias. Serum iron, total iron binding capacity, transferrin saturation, serum ferritin, serum transferrin receptor, transferrin receptor-ferritin index, and zinc-protoporhyrin concentration in erythrocytes are tests used for assessment of iron deficiency. The convention laboratory test for diagnosing iron deficiency is the measurement of serum ferritin. The most precise method for evaluating body iron stores is the examination for iron on aspirated bone marrow or marrow biopsy. Increased content of Hb A2 over 3.5% is diagnostic for beta-thalassemia. Presence of ringed sideroblasts is characteristic of sideroblastic anemias. Hemoglobin electrophoresis is required for the diagnosis of hemoglobinopathy E. The optimal therapeutic regimen in iron deficiency anemia used in this country is to administer 100 mg of elemental iron twice daily separately from meals. Ferrous sulphate (Ferronat Retard tbl. or Sorbifer Dulures tbl.) which are slow-releasing iron formulations are preferred because of their low cost, high bioavailability and low side-effects. Parenteral iron therapy is justified only in patients who cannot absorb iron, who have blood losses that exceed the maximal absorptive capacity of their intestinal tract or who are totally intolerant of oral iron. However, parenteral iron therapy may be associated with serious and even fatal side-effects.
 ...
PMID:[Microcytic and hypochromic anemias]. 1563 79

Classic iron deficiency (ID) does not represent a challenge for the laboratory and physicians. The anemia that accompanies infection, inflammation, and cancer, commonly termed anemia of chronic disease (ACD), features apparently normal or increased iron stores. However, 20% of these patients have iron-restricted erythropoiesis (functional ID), an imbalance between the iron requirements of the erythroid marrow and the actual iron supply. Functional ID leads to a reduction in red cell hemoglobiniza-tion, causing hypochromic microcytic anemia. The diagnosis of functional ID in real time is based on measuring the hemoglobin content of reticulocytes. An examination of the biochemical markers of iron metabolism demonstrates weaknesses in the diagnosis of functional ID. We developed a diagnostic plot for the assessment of iron status in ACD and the detection of advancing ID in patients with ID, ACD, and the combined state of functional ID and ACD. The plot indicates the correlation between a marker of the iron supply for erythropoiesis (ie, the ratio of the soluble transferrin receptor value to the logarithm of the ferritin value) and the reticulocyte hemoglobin content and functions as a marker of iron demand. The diagnostic plot shows good selectivity for assessing the iron status of disease-specific anemias such as classic ID, end-stage renal failure, cancer-related anemia, and the anemia of infection and inflammation. The therapeutic implications of the diagnostic plot are to differentiate patients who should be administered oral iron supplements, recombinant human erythropoietin (r-HuEPO), or a combination of r-HuEPO and iron. The response of erythropoiesis to r-HuEPO depends on the iron supply and the proliferation of erythropoiesis. The lack of an increase or a decrease in reticulocyte hemoglobin levels indicates a nonresponder to r-HuEPO or functional ID.
 ...
PMID:Anemia of chronic disease: pathophysiology and laboratory diagnosis. 1579 May 48

Iron-regulatory proteins (IRPs) 1 and 2 posttranscriptionally regulate expression of transferrin receptor (TfR), ferritin, and other iron metabolism proteins. Mice with targeted deletion of IRP2 overexpress ferritin and express abnormally low TfR levels in multiple tissues. Despite this misregulation, there are no apparent pathologic consequences in tissues such as the liver and kidney. However, in the central nervous system, evidence of abnormal iron metabolism in IRP2-/- mice precedes the development of adult-onset progressive neurodegeneration, characterized by widespread axonal degeneration and neuronal loss. Here, we report that ablation of IRP2 results in iron-limited erythropoiesis. TfR expression in erythroid precursors of IRP2-/- mice is reduced, and bone marrow iron stores are absent, even though transferrin saturation levels are normal. Marked overexpression of 5-aminolevulinic acid synthase 2 (Alas2) results from loss of IRP-dependent translational repression, and markedly increased levels of free protoporphyrin IX and zinc protoporphyrin are generated in IRP2-/- erythroid cells. IRP2-/- mice represent a new paradigm of genetic microcytic anemia. We postulate that IRP2 mutations or deletions may be a cause of refractory microcytic anemia and bone marrow iron depletion in patients with normal transferrin saturations, elevated serum ferritins, elevated red cell protoporphyrin IX levels, and adult-onset neurodegeneration.
 ...
PMID:Microcytic anemia, erythropoietic protoporphyria, and neurodegeneration in mice with targeted deletion of iron-regulatory protein 2. 1583 3

Hereditary hyperferritinaemia-cataract syndrome (HHCS) is a relatively rare disorder with an autosomal dominant trait. It can be caused by various mutations within the iron responsive element (IRE) of the L-ferritin gene. These mutations result in an increased translation of L-ferritin mRNA and consequently the accumulation of L-ferritin in different fluids and tissues. HHCS patients present with an isolated hyperferritinaemia in the absence of any sign of iron overload. Early onset bilateral cataract, probably due to accumulation of ferritin crystals in the lens, is the only presenting clinical manifestation. Internists, especially gastrohepatologists, should be aware of this syndrome and differentiate it from haemochromatosis which is much more frequent, in order to avoid unnecessary imaging procedures, liver biopsies and an eventual venesection therapy, which will only lead to microcytic anaemia. In the present paper we report the first cases with HHCS diagnosed in Belgium. At diagnosis, the seven known affected members of three different families had ferritin levels between 603 and 3432 microg/l (normal < 150 microg/l), and this in combination with normal iron and transferrin values. All of them were known with early-onset bilateral cataract and our postulated diagnosis of HHCS was confirmed after genetic sequencing of the L-ferritin gene, which showed a C39U point mutation in the first family, and an A40G point mutation in the IRE loop segment in the two other families. The other investigated members of the three families had normal ferritin values, no history of early-onset cataract and genetic analyses could not reveal a mutation in the IRE of their L-ferritin gene. In current clinical practice, gastroenterologists should remember that elevated ferritin levels in the absence of documented iron overload is not haemochromatosis.
 ...
PMID:Hereditary hyperferritinaemia-cataract syndrome: a challenging diagnosis for the hepatogastroenterologist. 1621 40

The purpose of this study was to detect the frequency of iron deficiency anemia in women attending their first antenatal clinic at a Maternal and Child Health Clinic in Kubang Kerian, a district of Kelantan that is located on the East coast of Malaysia. A cross-sectional study was done over a two-month period and fifty-two Malay women were enrolled in this study. Red blood cell indices and serum ferritin were used as a screening tool for anemia and iron status. Eighteen patients (34.6%) were anemic. The majority were classified as having mild anemia (90%). Four of them had hypochromic microcytic anemia. Of 52 women, 7 had iron deficient erythropoiesis and 11 (61.1%) had iron deficient anemia. The prevalence of iron deficiency anemia in pregnant women was 21.2%, which is similar to other developing countries. The serum ferritin level was significantly associated with the hemoglobin level (p=0.003). Other red blood cell indices were not useful in predicting iron deficient erythropoiesis. It is important to detect iron deficient erythropoiesis during the first antenatal check-up, as it is an early manifestation of iron deficiency anemia. In conclusion, screening for iron deficient is recommended during first antenatal visit because iron deficiency anemia is still the leading cause of nutritional deficiency in pregnant women. This will initiate an early therapeutic intervention so as to reduce public health problem.
 ...
PMID:Anemia and iron status of Malay women attending an antenatal clinic in Kubang Kerian, Kelantan, Malaysia. 1643 62

DMT1 mediates the pH-dependent uptake of Fe(2+) from the diet in duodenal enterocytes and in most other cells. It transfers iron from the endosomes to the cytosol following the uptake of the transferrin-transferrin receptor complex. DMT1 mutations are responsible for severe hypochromic microcytic anemia in rodents and in 2 human patients described recently. We report a compound heterozygote for 2 new DMT1 mutations, associated with microcytic anemia from birth and progressive liver iron overload. The first mutation is a GTG deletion in exon 5, leading to the V114 in-frame deletion in transmembrane domain 2, and the second is a G --> T substitution in exon 8 leading to the G212V replacement in transmembrane domain 5. Together with the 2 previously reported cases, this patient defines a new syndrome of congenital microcytic hypochromic anemia, poorly responsive to oral iron treatment, with liver iron overload associated paradoxically with normal to moderately elevated serum ferritin levels.
 ...
PMID:Two new human DMT1 gene mutations in a patient with microcytic anemia, low ferritinemia, and liver iron overload. 1643 78

Iron regulatory proteins 1 and 2 (IRPs) are homologous mammalian cytosolic proteins that sense intracellular iron levels and post-transcriptionally regulate expression of ferritin, transferrin receptor, and other iron metabolism proteins. Adult mice with homozygous targeted deletion of IRP2 develop microcytic anemia, elevated red cell protoporphyrin IX levels, high serum ferritin, and adult-onset neurodegeneration. Mice with homozygous deletion of IRP1 develop no overt abnormalities, but mice that lack both copies of IRP2 and one copy of IRP1 develop a more severe anemia and neurodegeneration than mice with deletion of IRP2 alone. Here, we have demonstrated that IRP1-/- IRP2-/- embryos do not survive gestation, and that although IRP1-/- IRP2-/blastocysts can be genotyped and harvested, implanted embryos with the IRP1-/- IRP2-/genotype are undetectable at embryonic day 6.5 and beyond. Blastocysts derived from a cross in which 25% of the fertilized embryos were expected to have the IRP1-/- IRP2-/genotype often showed brown discoloration and abnormal morphology. These abnormal blastocysts likely have the IRP1-/- IRP2-/- genotype, and the brown discoloration may be attributable to ferritin overexpression and sequestration of ferric iron in ferritin, whereas abnormal morphology may be due to concomitant functional iron deficiency. These results demonstrate that IRPs are indispensable for regulation of mammalian iron homeostasis at the post-implantation stage of murine embryonic development.
 ...
PMID:Complete loss of iron regulatory proteins 1 and 2 prevents viability of murine zygotes beyond the blastocyst stage of embryonic development. 1648 Sep 4

The prevalence of iron deficiency anemia is 2 percent in adult men, 9 to 12 percent in non-Hispanic white women, and nearly 20 percent in black and Mexican-American women. Nine percent of patients older than 65 years with iron deficiency anemia have a gastrointestinal cancer when evaluated. The U.S. Preventive Services Task Force currently recommends screening for iron deficiency anemia in pregnant women but not in other groups. Routine iron supplementation is recommended for high-risk infants six to 12 months of age. Iron deficiency anemia is classically described as a microcytic anemia. The differential diagnosis includes thalassemia, sideroblastic anemias, some types of anemia of chronic disease, and lead poisoning. Serum ferritin is the preferred initial diagnostic test. Total iron-binding capacity, transferrin saturation, serum iron, and serum transferrin receptor levels may be helpful if the ferritin level is between 46 and 99 ng per mL (46 and 99 mcg per L); bone marrow biopsy may be necessary in these patients for a definitive diagnosis. In children, adolescents, and women of reproductive age, a trial of iron is a reasonable approach if the review of symptoms, history, and physical examination are negative; however, the hemoglobin should be checked at one month. If there is not a 1 to 2 g per dL (10 to 20 g per L) increase in the hemoglobin level in that time, possibilities include malabsorption of oral iron, continued bleeding, or unknown lesion. For other patients, an endoscopic evaluation is recommended beginning with colonoscopy if the patient is older than 50.
 ...
PMID:Iron deficiency anemia. 1972 82

The iron deficiency is the first cause of anaemia. In healthy young adult, anemia is well tolerated because of its progressive installation. The most common symptoms of anemia are pallor, fatigue and dyspnea. In biological exams, anemia is classically associated with microcytosis and hypochromia. The origins of microcytic anemia are iron deficiency, inflammatory aetiologies, thalassemia and sideroblastic anaemia. The iron-deficiency diagnosis includes two explorations: biological and clinical. The biological exploration is based on interpretation of serum biologics tests as blood iron, ferritin, transferrin with saturation, total iron-binding capacity and its soluble receptors. This interpretation is simple if it is not associated with clinical disorders influencing the internal iron cycle. The clinical exploration must always be followed by a careful assessment of the underlying cause as blood loss. The most common causes in women of reproductive age are gynaecologic. In men and menopausal women, the gastrointestinal tract bleeding is source of anemia. Therapeutic management of anemia is oral iron therapy. Etiological diagnostic of microcytosis is essential before iron therapy. If not, the treatment could be inefficient or it could mask or delay the etiological diagnostic.
 ...
PMID:[Iron deficiency anaemia: clinical presentation, biological diagnosis and management]. 1749 37

Erythropoietic protoporphyria (EPP) results from deficiency of ferrochelatase (FECH). Accumulation of protoporphyrin IX causes life-long acute photosensitivity. Microcytic anemia occurs in 20% to 60% of patients. We investigated 178 patients with dominant EPP confirmed by molecular analysis. Erythropoiesis was impaired in all patients; all had a downward shift in hemoglobin (Hb), and the mean decreased in males by 12 g/L (1.2 g/dL). By World Health Organization criteria, 48% of women and 33% of men were anemic. Iron stores, assessed by serum ferritin (sFn), were decreased by two-thirds, but normal serum soluble transferrin receptor-1 and iron concentrations suggested that erythropoiesis was not limited by iron supply. FECH deficiency in EPP appears to lead to a steady state in which decreased erythropoiesis is matched by reduced iron absorption and supply. This response may in part be mediated by protoporphyrin, but we found no correlation between erythrocyte protoporphyrin and Hb, sFn, total iron-binding capacity, or transferrin saturation.
 ...
PMID:Erythropoiesis and iron metabolism in dominant erythropoietic protoporphyria. 1780 93


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