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Query: UMLS:C0240066 (iron deficiency)
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This paper is written in the context of our changing perception of the immunological system as a system with possible biological roles exceeding the prevailing view of a system concerned principally with the defense against external pathogens. The view discussed here relates the immunological system inextricably to the metabolism of iron, the circulation of the blood and the resolution of the evolutionary paradox created by oxygen and iron. Indirect evidence for this inextricable relationship between the two systems can be derived from the discrepancy between the theoretical quasi-impossibility of the existence of an iron deficiency state in the adult and the reality of the WHO numbers of people in the world with iron deficiency anemia. With the mounting evidence that TNF, IL-1, and T lymphocyte cytokines affect hemopoiesis and iron metabolism it is possible that the reported discrepancy is a reflection of that inextricable interdependence between the two systems in the face of infection. Further direct evidence for a relationship between T cell subset numbers and iron metabolism is presented from the results of a study of T cell populations in patients with hereditary hemochromatosis. The recent finding of a correlation between low CD8+ lymphocyte numbers, liver damage associated with HCV positivity and severity of iron overload in beta-thalassemia major patients (unpublished data of RW Grady, P. Giardina, M. Hilgartner) concludes this review.
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PMID:T lymphocytes and iron overload: novel correlations of possible significance to the biology of the immunological system. 134 13

Although iron supplementation is considered beneficial for groups at risk for anemia, concern has been raised that it could be harmful during human immunodeficiency virus (HIV) infection. Studies suggest: (1) faster HIV disease progression in thalassemia major patients receiving inadequate doses of iron-chelating drug; (2) higher mortality among patients receiving iron supplementation with dapsone compared with aerosolized pentamidine for prophylaxis against Pneumocytis carinii pneumonia; (3) higher iron stores and mortality among patients with haptoglobin Hp 2-2 phenotype; and (4) shorter survival among patients with high bone marrow iron deposition. These studies largely involved men in developed countries. Among HIV-infected pregnant women in Africa with a high prevalence of iron deficiency, no relationship was found between indicators of iron status and HIV disease severity. The available data do not contraindicate the current practice of iron supplementation in developing countries where there is a high prevalence of both HIV infection and iron deficiency.
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PMID:Iron supplementation during human immunodeficiency virus infection: a double-edged sword? 1160 73

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.
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PMID:Iron deficiency and overload. 1463 76

Most of the techniques for measuring iron stores such as serum iron concentration, iron binding capacity, serum ferritin level, liver biopsy can be troublesome or invasive for patients with thalassemia. The salivary iron measurement could be of potential advantage being an easy and non invasive approach for diagnosis of iron deficiency and iron overload . The aim of this study was to compare the levels of iron and ferritin in saliva and serum of patients affected by thalassemia or iron deficiency anemia. For this purpose, 96 patients with iron overload (71 with thalassemia major, 10 with thalassemia intermedia and 15 with thalassemia trait), 30 patients with iron deficiency anemia, and 35 healthy children as control group were involved in this study. Their saliva and serum iron and ferritin levels were measured. Iron and ferritin levels were higher in iron overload groups than in control group and lower in iron deficiency group (p<0.05). Furthermore serum and saliva iron and ferritin levels paralleled in all groups. In conclusion, iron and ferritin saliva can be routinely used for diagnosis of both iron overload and deficiency; furthermore this procedure may be an important advantage for blood donors being easily available and not invasive.
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PMID:Iron and ferritin levels in saliva of patients with thalassemia and iron deficiency anemia. 2297 95

Iron metabolism is a balancing act, and biological systems have evolved exquisite regulatory mechanisms to maintain iron homeostasis. Iron metabolism disorders are widespread health problems on a global scale and range from iron deficiency to iron-overload. Both types of iron disorders are linked to heart failure. Iron play a fundamental role in mitochondrial function and various enzyme functions and iron deficiency has a particular negative impact on mitochondria function. Given the high-energy demand of the heart, iron deficiency has a particularly negative impact on heart function and exacerbates heart failure. Iron-overload can result from excessive gut absorption of iron or frequent use of blood transfusions and is typically seen in patients with congenital anemias, sickle cell anemia and beta-thalassemia major, or in patients with primary hemochromatosis. This review provides an overview of normal iron metabolism, mechanisms underlying development of iron disorders in relation to heart failure, including iron-overload cardiomyopathy, and clinical perspective on the treatment options for iron metabolism disorders.
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PMID:Role of iron metabolism in heart failure: From iron deficiency to iron overload. 3110 56