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INTRODUCTION

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SUMMARY

Iron deficiency and iron-deficiency anemia are common nutritional and hematologic disorders. In infants and young children, iron deficiency is most commonly caused by insufficient dietary iron. Rarely, it can result from mutations in TMPRSS6, a gene encoding a membrane protease that serves normally as a transcriptional suppressor of the primary negative regulator of iron absorption, hepcidin. In young women, iron deficiency is most often the result of blood loss in menstruation or as a result of blood loss during pregnancy, childbirth, and lactation. In older adults, bleeding is often the cause of iron deficiency, and may originate from the gastrointestinal tract, as from hemorrhoids, peptic ulcer, hiatus hernia, colon cancer, or angiodysplasia; from the genitourinary tract; from uterine leiomyomas or carcinoma, or a renal tumor; or from the pulmonary tree, through chronic hemoptysis caused by infection or malignancy, or as a result of idiopathic pulmonary hemosiderosis. Iron deficiency in infants can result in impairment of growth and intellectual development. The hematologic features of iron deficiency are nonspecific and too often confused with other causes of microcytic anemia such as thalassemias, chronic inflammation, and renal neoplasms. A low serum ferritin concentration is a good indicator of iron deficiency, but ferritin levels are increased by inflammation and can be particularly high in cancer, macrophage activation syndromes, hepatitis, or chronic kidney disease, which may mask the detection of iron deficiency coexisting with the anemia of chronic inflammation. The plasma iron is decreased and the iron-binding capacity increased in severe iron deficiency, but these alterations are not uniformly present in mild iron deficiency, and low plasma iron levels are also characteristic of the anemia of inflammation. Other laboratory tests that are useful include assays for serum transferrin receptor, reticulocyte hemoglobin content, percent hypochromic erythrocytes and erythrocyte zinc protoporphyrin. Diagnosis of iron deficiency, particularly in an adult, obliges the clinician to determine the site and cause of blood loss, and to rectify it whenever possible. Ferrous salts, in doses of 100 to 200 mg of elemental iron daily, are the initial treatment in most patients with iron deficiency. Enteric-coated and prolonged-release preparations should be avoided. Complete correction of anemia is expected in 8 to 12 weeks, depending on patient’s age. If this response is not achieved, the patient and the diagnosis require reevaluation. Administration of iron should be continued for 12 months after correction of anemia, or for as long as bleeding continues. Parenteral iron is used in patients who need more iron than can be delivered by the oral route, patients who do not tolerate oral iron salts, patients with gastrointestinal disease or following certain forms of bariatric surgery, noncompliant patients, and patients undergoing renal dialysis. All current parenteral iron preparations are much less likely to cause serious adverse events than was the case for high-molecular-weight iron dextran used in the past.

At the opposite end of the iron disorder spectrum, iron storage disease (hemochromatosis) can be the result of mutations of genes that ...

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