Idiopathic hemochromatosis

Slegelman, E.S., Mitchell, D.G., Cutwater, E., Munoz, S.J., Rubin, R. Idiopathic hemochromatosis MR imaging findings in cirrhotic and precirrhotic patients. Radiology 1993 188 637-641... 

Blumberg, R.S., Chopra, S., Ibrahim, R., Crawford, X, Farraye, F.A., Zeldis, XB., Berman, M.D. Primary hepatocellular carcinoma in idiopathic hemochromatosis after reversal of cirrhosis. Gastroenterology 1988 95 1399-1402... 

Nouel O, Voisin PM, Vaucel J, Dartois-Hoguin M, Le Bris M. Association d une septicemic a Yersinia enterocolitica, d une hemochromatose idiopathique et d un traitement par deferoxamine. [Yersinia enterocolitica septicemia associated with idiopathic hemochromatosis and deferoxamine therapy. A case.] Presse Med 1991 20(31) 1494-6. 

In some adults, iron overload can be the result of a genetic defect (idiopathic hemochromatosis) that causes malfunction of the normal homeostasis mechanism and, in turn, excessive absorption of iron. Iron overload can also be caused by too many blood transfusions, which results in too much iron in the various iron-containing organs. 

Hereditary hemochromatosis is the most common hereditary form of hemochromatosis. It results from hereditary abnormalities of proteins that regulate iron hemosta.sis. In recent years, the genetic lesions responsible for many forms of the disease have been discovered. It is an adult onset disorder, formerly called primary hemochromatosis or idiopathic hemochromatosis, which is linked to the HLA loci on chromosome 6. 

In 1976 Simon et al reported an association of human leukocyte antigen (HLA)-A3 and HLA-B14 antigens with idiopathic hemochromatosis, which suggested that the HH gene was located near the major histocoinpatibility complex (MHC) on chromosome 6p (short arm of chromosome gj 409,532 genetic studies confirmed linkage of the HH... 

Lalouel JM, Le Mignon L, Simon M, Fauchet R, Bourel M, Rao DC, et al. Genetic analysis of idiopathic hemochromatosis using both qualitative (disease status) and quantitative (serum iron) mformation. Am J Hum Genet 1985 37 700-18. 

Homeostatic mechanisms are very important for the prevention of accumulation of excess Fe that is believed to generate oxidative stress by catalysis of variety of chemical reactions involving free radicals, which could result in cell damage (Pietrangelo, 2002 Puntarulo, 2005). Excess Fe accumulation may promote cancer and increase the cardiovascular risk (Martmez-Navarrete et ah, 2002). Iron overload can be observed in some cases including an excessive dietary iron intake, inherited diseases, for example, idiopathic hemochromatosis, congenital atransferrinemia, or the medical treatment of thalassemia (Fontecave and Pierre, 1993). 

Values reported as xg iron per 100 mg dry weight for controls ranged from 34.4 to 136.4 with a mean ( SD) of 77.7 ( 9.7) in males and 72.6 ( 13.6) in females [56]. These levels increase about 25- to 40-fold in idiopathic hemochromatosis and thalassemia major. If one analyzes liver without drying, the values obtained are about 25% of those found with nonfatty dry tissue [58]. 

MacDonald, R.A. Idiopathic hemochromatosis Genetic or acquired Arch, intern. Med. 112, 184-190(1963)... 

It is conceivable that iron-catalyzed reactions could occur in some diabetic individuals, since diabetes is found commonly in patients with transfusion siderosis, dietary iron overload, and idiopathic hemochromatosis (McLaren et al, 1983 Phelps et al, 1989). This suggestion is further supported by the observation that desferrioxamine treatment decreases hyperglycemia and lowers hypercholesterolemia and hyperlipidemia in diabetic patients with high ferritin but no hemachromatosis (Cutler, 1989). 

Ascorbate may also have detrimental effects related to its role in iron mobilization. Iron overload can occur as a result of high dietary iron, blood transfusion, or idiopathic hemochromatosis (Nienhuis, 1981 Murray, 1982 Halliwell, 1983 Hal-liwell and Gutteridge, 1989). 

Grootveld M, Bell JD, Halliwell B, Aruoma OI, Bomford A, Sadler PJ (1989) Nontransferrin-bound iron in plasma or serum from patients with idiopathic hemochromatosis. Characterization by high performance liquid chromatography and nuclear magnetic resonance spectroscopy. J Biol Chem 264 4417-4422 Gyparaki M, Porter JB, Huehns ER, Hider RC (1986) Evaluation in vivo of hydro-xypyrid-4-one iron chelators intended for the treatment of iron overload by the oral route. Biochem Soc Trans 14 1181-1181 Hallaway PE, Eaton JW, Panter SS, Hedlund BE (1989) Modulation of deferoxamine toxicity and clearance by covalent attachment to biocompatible polymers. Proc Natl Acad Sci USA 86 10108-10112... 

Taken together, hepatic cirrhosis of any etiology represents the major risk factor for HCC with additional increased incidence in viral hepatitis and idiopathic hemochromatosis (El-Serag and Mason 2000). 

Iron overload may occur as a result of metabolic defects, such as idiopathic hemochromatosis—an inherited disease, or from high intakes of iron. The clinical signs and symptoms of iron overload may include hyperpigmentation of the skin, cirrhosis of the liver, diabetes, and myocardial failure. Dr. John R. K. Robson, M.D., one of the coauthors of this book, has observed excessive intakes of iron, characterized by hemosiderosis and cirrhosis of the liver, in the Bantu tribe of South Africa who cook their food in iron pots and ferment their beer in iron utensils—and who have iron intakes of up to 100 mg, or more, per day. 

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