Hemochromatosis

Transferrin is essential for movement of iron and without it, as in genetic absence of transferrin, iron overload occurs in tissues. This hereditary atransferrinemia is coupled with iron-deficiency anemia. The iron overload in hereditary or acquired hemochromatosis results in fully saturated transferrin and is treated by phlebotomy (10). 

The special interest is the determination of Fe, as the acceleration of sclerosed process is connected with the accumulation of Fe in this organ. Copper is accumulated in tissues at the genetic caused diseases (Wilson Disease, Hemochromatosis). This is the alteration in elemental ratios (e.g., Cu/Zn), that is the marker of pathological process. 

Wilson, I.A., Bjorkman, P.J. Unusual MHC-like molecules CDl, Pc receptor, the hemochromatosis gene product, and viral homologs. Curr. Opin. Struct. Biol. 10 67-73, 1998. 

Although iron deficiency is a common problem, about 10% of the population are genetically at risk of iron overload (hemochromatosis), and elemental iron can lead to nonen2ymic generation of free radicals. Absorption of iron is stricdy regulated. Inorganic iron is accumulated in intestinal mucosal cells bound to an intracellular protein, ferritin. Once the ferritin in the cell is saturated with iron, no more can enter. Iron can only leave the mucosal cell if there is transferrin in plasma to bind to. Once transferrin is saturated with iron, any that has accumulated in the mucosal cells will be lost when the cells are shed. As a result of this mucosal barrier, only about 10% of dietary iron is normally absorbed and only 1-5% from many plant foods. 

Ferritin is another protein that is important in the metabolism of iron. Under normal conditions, it stores iron that can be called upon for use as conditions require. In conditions of excess iron (eg, hemochromatosis), body stores of iron are greatly increased and much more ferritin is present in the tissues, such as the liver and spleen. Ferritin contains approximately 23% iron, and apoferritin (the protein moiety free of iron) has a molecular mass of approximately 440 kDa. Ferritin is composed of 24 subunits of 18.5 kDa, which surround in a micellar form some 3000-4500 ferric atoms. Normally, there is a little ferritin in human plasma. However, in patients with excess iron, the amount of ferritin in plasma is markedly elevated. The amount of ferritin in plasma can be conveniently measured by a sensitive and specific radioimmunoassay and serves as an index of body iron stores. 

Hereditary (primary) hemochromatosis is a very prevalent autosomal recessive disorder in certain parts of the world (eg, Scodand, Ireland, and North America). It is characterized by excessive storage of iron in tissues, leading to tissue damage. Total body iron ranges between 2.5 g and 3.5 g in normal adults in primary hemochromatosis it usually exceeds 15 g. The accumulated iron... 

HFE has been shown to be located in cells in the crypts of the small intestine, the site of iron absorption. There is evidence that it associates with P2 niicroglobu-lin, an association that may be necessary for its stability, intracellular processing, and cell surface expression. The complex interacts with the transferrin receptor (TfR) how this leads to excessive storage of iron when HFE is altered by mutation is under close smdy. The mouse homolog of HFE has been knocked out, resulting in a potentially useful animal model of hemochromatosis. 

A scheme of the likely main events in the causation of hereditary hemochromatosis is set forth in Figure 50-5. 

Figure SOS. Tentative scheme of the main events in causation of primary hemochromatosis (MIM 235200). The two principal mutations are CY282Y and H63D (see text). Mutations in genes other than HFE are also involved in some cases.

Transferrin binds iron, transporting it to sites where it is required. Ferritin provides an intracellular store of iron. Iron deficiency anemia is a very prevalent disorder. Hereditary hemochromatosis has been shown to be due to mutations in HFE, a gene encoding the protein HFE, which appeats to play an important role in absorption of iron. 

Waheed A et al Regulation of transferrin-mediated iron uptake by HFE, the protein defective in hereditary hemochromatosis. Proc Natl Acad USA 2002 99 3117. 

Hereditary hemochromatosis is an autosomal recessive disease of increased intestinal iron absorption and deposition in hepatic, cardiac, and pancreatic tissue. Hepatic iron overload results in the development of fibrosis, hepatic scarring, cirrhosis, and hepatocellular carcinoma. Hemochromatosis can also be caused by repeated blood transfusions, but this mechanism rarely leads to cirrhosis. 

Metabolic disorder (hemochromatosis, ochronosis, Wilson s disease, chondrocalcinosis, Paget s disease)... 

Ramm, G.A. (2000). In Hemochromatosis. Genetics, Pathophysiology, Diagnosis and Treatment (eds Barton, J.C. and Edwards, C.Q.), Cambridge University Press, Cambridge, pp. 494-507. 

Iron is an extremely important element present in all living organisms correspondingly, iron metabolism is well studied. Both iron deficiency and iron excess are origins of serious pathologies (iron-deficit anemias, hereditary hemochromatosis, thalassemia, etc.) associated with the overproduction of oxygen radicals. Free radical-mediated processes, characteristic of these pathologies, are considered in Chapter 31 here we will look at some mechanisms of toxic effects of iron. 

Metabolic liver disease Hemochromatosis Wilson s disease < 1-Antitrypsin deficiency Nonalcoholic steatohepatitis ("fatty liver")... 

When the post-coagulation sludge is added to hydrolyzate production, then the iron hydroxide is converted into ferric sulfate, which is well soluble in water. Too high content of soluble iron compounds, which are easily absorbable, should be avoided, as the excessive amount of the iron in the diet is harmful [13]. It leads to some disease like hemochromatosis or siderosis. Thus, the aim of our research was to find a method of decreasing the absorbable iron content of fish silage. 

Heart attack A seizure of weak or abnormal functioning of the heart. [NIH] Hemochromatosis A disease that occurs when the body absorbs too much iron. The body... 

Other examples of single-gene diseases with delayed age of onset include familial breast cancer, familial colon cancer, adult polycystic kidney disease, and hemochromatosis. 

A man is a known heterozygous carrier of a mutation that causes hemochromatosis (autosomal recessive disease). Suppose that 1% of the general population consists of homozygotes for this mutation. If the man mates with somebody from the general population, what is the probability that he and his mate will produce a child who is an affected homozygote ... 

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