Iron storage disease

Use iron complex former (for therapy of iron storage diseases)... 

Deferiprone has a concentration-dependent affinity for iron, with a higher binding constant than deferoxamine or diethylenetriaminepentaacetic acid (DTPA). However, it takes three molecules of deferiprone to bind one molecule of iron, whereas deferoxamine binds iron in a 1 1 ratio. For this reason, deferiprone must be present in very high concentrations, close to toxic concentrations, to be effective (2). Deferiprone dissociates from iron when its concentration in body fluids falls to the concentration achieved just a few hours after oral administration (3). Deferiprone is effective in excreting iron in iron storage diseases and aluminium in patients on hemodialysis (1). 

Deferoxamine is used in the treatment of acnte iron poisoning and in iron storage diseases, notably beta-thalassemia (1). The usual regimen is 40mg/kg/day as a snbcntaneous infusion over 10-12 honrs, starting at an early age (3 years). During erythrocyte transfusion. 

In iron storage disease, ascorbic acid should be given only after adequate serum concentrations of deferoxamine have been attained, in order to prevent serious cardiac arrhythmia (14). Opportunistic fungal infections associated with deferoxamine may also involve the heart muscle and usually have a fatal outcome (15-17). 

In one prospective study in 17 patients with hemoljdic anemia (aged 5-25 years) lens opacities were found in 41%, changes in the retinal pigment epithelium in 35%, tortuosity of retinal vessels in 24%, dilatation and sheathing of retinal vessels in 18%, defects in color vision in 29%, and abnormal dark adaptation in 18% (56). In many other studies much lower frequencies were found. Perhaps retinal injury is related to the depletion of metals such as zinc, copper, and/or iron (57). On the other hand, ocular and auditory disturbances are not infrequent in patients with thalassemia, iron storage diseases (58,59), or uremia (45), and may be coincidental in patients receiving deferoxamine (60). 

Hemosiderosis, hemochromatosis, and some anemias are conditions associated with iron overload and iron storage diseases. 

A dominantly inherited form of iron storage disease results from mutations in ferroportin (SLCllAS). Here iron storage occurs primarily in macrophages, not in liver parenchyma. Iron accumulation appears to be more common in Africans than Europeans, and although diet may play a major role, it is thought that there is also a genetic predisposition that may account for the increased iron burden. ... 

Measurement of serum ferritin levels has diagnostic utility. In iron deficiency anemia (discussed later), serum ferritin levels are low in iron storage disease, the levels are high. However, serum ferritin levels can also be elevated under many other circumstances, including liver diseases and chronic inflammatory diseases. 

In iron storage diseases accompanied by normal erythropoiesis (e.g., hereditary hemochromatosis), removal of excessive iron is accomplished by repeated bloodletting (phlebotomy). Therapeutic phlebotomy of a unit of blood (which contains about 250 mg of iron) may be performed up to three times per week. When the iron stores become depleted, reaccumulation of iron is prevented by four to six phlebotomies per year. In asymptomatic patients, periodic determination of serum ferritin provides a measure of storage of iron. 

As previously noted for ferrous glycinate (Annex 1, reference 166), products, including sodium iron EDTA, that are intended to provide a source of additional iron should not be consumed by individuals with any type of iron storage disease, except under medical supervision. 

Iron storage diseases (hemochromatosis, multiple transfusions) Acute and chronic inflammations Liver diseases... 

There shouid be an awareness that iarge doses of vitamin C are known to increase (1) the urinary output of oxaiic acid and uric acid, and (2) the intestinai absorption of iron. Thus, massive doses of vitamin C may be hazardous to those with a iiabiiity to kidney stones or iron-storage disease. 

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