Diseases of iron overload: causes, symptoms, diagnosis, treatment

When iron (Fe) enters in amounts exceeding the body's requirements, it is deposited in tissues as hemosiderin. The deposition of iron leads to tissue damage (with a total iron content in the body> 5 g) and is called hemochromatosis. Local or generalized deposition of iron without tissue damage is called hemosiderosis. Diseases of iron overload can be primary (genetically determined) in violation of iron metabolism or secondary, caused by other diseases, in which the intake or release of iron increases. Iron can accumulate in almost all tissues, but most often pathological changes develop with the deposition of iron in the liver, the thyroid gland, the pituitary gland, the hypothalamus, the heart, the pancreas and joints. The defeat of the liver leads to an increase in the level of aminotransferases (ALT and ACT), fibrosis and cirrhosis.

[1], [2], [3], [4], [5], [6], [7], [8]

Hemosiderosis

Local hemosiderosis can be caused by recurrent hemorrhages in the organ. Iron released from erythrocytes can lead to a significant deposition in the tissues of hemosiderin. The most commonly affected organ is the lung, which is caused by recurrent pulmonary hemorrhage, both idiopathic (for example, Goodpasture's syndrome) and conditioned chronic pulmonary hypertension (eg primary pulmonary hypertension, pulmonary fibrosis, severe mitral stenosis). Sometimes loss of iron leads to the development of iron deficiency anemia, since iron in tissues can not be re-used.

Renal hemosiderosis can be the result of intense intravascular hemolysis. Free hemoglobin is filtered in the renal glomeruli, and the iron is deposited in the kidneys. Parenchyma of the kidneys is not damaged, but expressed hemosiderinuria can lead to iron deficiency.

Ferroportin's disease

Ferroporin's disease is found mainly among the inhabitants of the south of Europe and is the result of an autosomal dominant mutation of the SLC 40 A1 gene. The disease manifests itself in the first decade of life by increasing the serum ferritin level with a low or normal content of transferrin with a progressive increase in transferrin saturation in the 3rd and 4th decades of life. Clinical manifestations are lighter than those with NDA disease and include mild liver damage and mild anemia. Large phlebotomies are not well tolerated, monitoring of hemoglobin level and transferrin saturation is necessary.

[9], [10], [11]

Deficiency of transferrin and ceruloplasmin

With a deficiency of transferrin, absorbed iron, not associated with transferrin, enters the portal system and is deposited in the liver. The subsequent transfer of it to the place of production of red blood cells is reduced due to a deficiency of transferrin. With a shortage of ceruloplasmin, there is a shortage of ferroxidase, leading to a disruption in the conversion of ferrous iron to trivalent iron, which is necessary for binding to transferrin, which disrupts the transport of iron from the intracellular pool to the blood plasma, causing iron accumulation in the tissues.

Impaired iron transport is suspected in patients with iron overload, which develops at an early age, or when signs of iron overload are detected, but genetic studies show no abnormalities. The diagnosis is based on the determination of serum transferrin (or iron binding ability) and ceruloplasmin. Treatment is experimental.

The autosomal recessive form of hemochromatosis can be caused by a mutation of the transferrin receptor 2, a protein controlling the transferrin saturation. Symptoms and symptoms are similar to HFE hemahromatosis .

[12], [13], [14], [15], [16], [17], [18], [19],

Secondary Iron Overload

Secondary iron overload can develop with thalassemia or sideroblastic anemia, which are diseases of erythropoiesis. Secondary acquired overload may occur after exogenous iron administration with repeated massive blood transfusions or with the treatment of iron dextran. Each dose of transfused blood provides intake of 250 mg of iron. Significant deposits of iron are possible when administered> 20 g (ie, about 80 doses of blood). Iron overload can occur due to abnormal erythropoiesis with thalassemia, sideroblastic anemia, hemoglobinopathies and anomalies of erythrocyte enzymes. If there is a violation of erythropoiesis, there is an increase in the absorption of iron, possibly due to pepsidine. Violation of erythropoiesis can be detected by studying the patient's anamnesis. Iron overload is determined by increasing serum iron, saturation of transferrin and serum ferritin.

Phlebotomies may not always be indicated, as these diseases are often accompanied by anemia, which limits the possibility of exfusion of sufficient blood. In the presence of anemia, deferoxamine is used [1-2 g daily for 8-24 h in adults; 20-40 mg / (kg-day) for 8-24 hours in children], which should be administered as a slow intravenous infusion overnight, 5-7 days per week, which effectively reduces iron stores. With therapy with deferoxamine, tachyphylaxis can occur, so the effectiveness of therapy should be controlled (usually determining the iron in the urine). The red color of urine indicates the withdrawal of more than 50 mg of iron per day. The goal of treatment and monitoring (with serum iron and transferrin levels) is the same as in primary hemochromatosis.

Iron overloading of an unclear reason

Parenchymal diseases of the liver, alcoholic liver disease, non-alcoholic steatohepatitis and chronic hepatitis C can be associated with an elevated iron content in the body. The mechanism of the disorder is unknown, although the existence of a primary hemochromatosis, which should be excluded, is also possible. If patients do not have primary hemochromatosis, a decrease in iron content does not improve liver function.