Genetic diseases hemochromatosis

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. 

Individuals at risk for developing a genetic disease with a delayed age of onset may wish to learn whether they have inherited a disease-causing mutation (e.g., Huntington disease, femilial breast cancer, hemochromatosis, adenomatous polyposis coli). In some cases, presymptomatic diagnosis can be highly usefiil in preventing serious disease consequences before they occur (e.g., phlebotomy for hemochromatosis, early tumor detection for familial breast cancer). 

Caucasian. In the United States, most testing clients are, like the majority of the population, Caucasian non-Jews. This is important for the testing laboratory to know because the Bayesian for carrying a common disease allele, such as that causing cystic fibrosis, differs from that of Ashkenazi Jews, Asians, or African Americans. In addition, Caucasian non-Jews of Northern European descent are more prone to different genetic diseases, such as hemochromatosis, than are individuals of other ethnicities. 

Hemochromatosis is a condition in which the body accumulates excess amounts, of iron it is one of the most common genetic diseases in humans. The symptoms of hemochromatosis include the classic triad of bronzing of the skin, cirrhosis, and diabetes. Other manifestations include cardiomyopathies and arrhythmias, endocrine deficiencies, and possibly arthropathies. 

The transmembrane transport of iron into eukaryotic cells was not well defined when these studies began. In fact, a eukaryotic iron transporter had not yet been identified. Even within the well-characterized manunalian transferrin-dependent iron transport system, the mechanism of transmembrane iron transport from the endosomal lumen into the cytosol was unknown [6]. It is important to characterize eukaryotic iron transport since disruption of iron homeostasis in humans results in disease. Anemia, due to iron deficiency is a serious health problem [7]. In addition, the common genetic disease hereditary hemochromatosis results, excess iron absorption from the gut which causes iron overload [8]. The excess iron accumulates... 

Hepatic zinc levels are elevated in patients with hemochromatosis, a genetic disease associated with increased iron absorption from the intestine (Adams et al. 1991). The chronic iron loading that occurs could result in hepatic metallothionein induction leading to the accumulation of zinc because metallothionein has a greater affinity for zinc than iron. These individuals may, therefore, have a greater likelihood of developing toxicity with zinc exposure levels that do not normally result in any symptoms in the general population. 

Iron deficiency is one of the most common nutrient deficiencies in the world, occurring in up to 60% of the women, infants, and children of some countries. Anemia, characterized by a low concentration of hemoglobin in the blood or by a low volume of packed red blood cells, is the usual symptom of iron deficiency. Other symptoms include fatigue and cognitive disorders. Up to 1% of the population may have the genetic disease known as hereditary hemochromatosis, which results in excess absorption of dietary iron and can lead to liver and heart damage. Con-... 

Individuals with a family history of an autosomal or X-linked recessive disease may wish to know whether they are a heterozygous carrier of the disease. This can be established by genetic diagnosis (e.g., for cystic fibrosis, hemochromatosis, PKU, or albinism). In some specific cases, a population at high risk for a specific disease may be screened for carrier status using genetic diagnosis (e.g., Tay-Sachs disease in the Jewish population [see Clinical Correlate]). 

Sallie, R.W., Reed, W.D., Shilkin, K.B. Confirmation of the efficacy of hepatic tissue iron index in differentiating genetic hemochromatosis from alcoholic liver disease complicated by alcoholic hemosiderosis. Gut 1991 32 207-210... 

Iron-overload disease, or hemochromatosis, may occur as a consequence of an, as yet, undefined genetic defect, or as a secondary effect of another medical disorder, such as thalassemia. In the former condition, primary hemochromatosis, iron accumulates in various tissues because of a lack of control of iron absorption from the gut. In the latter, or secondary hemochromatosis, the accumulation of iron results from the breakdown of red blood cells and the consequent need for frequent blood transfusions, which lead to an increase in the levels of tissue iron. In both cases the predominant store for iron is hemosiderin (147). 

Although genetic defects in the metahoUsm of trace elements are rare, they are nonetheless important because of the information they have provided as to homeostatic control mechanisms. This in turn has led to development of effective therapeutic strategies. The most commonly investigated disorders are those affecting iron (hemochromatosis), copper (Wilson s disease and Menkes syndrome), zinc (acrodermatitis enteropathica), and molybdenum (molybdenum cofactor disease). 

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. 

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. 

Restrictive myocardial disease may result from several local or systemic disorders. Amyloidosis, hemochromatosis, scleroderma, carcinoid, sarcoidosis, diabetes, pseudoxanthoma elasticum, and endomyocardial fibrosis have been known to cause restrictive cardiomyopathy. The most common cause of restrictive cardiomyopathy in the industrialized world is amyloidosis, whereas endomyocardial fibrosis is a common cause in tropical areas of the world. There may be a genetic predisposition to idiopathic restrictive cardiomyopathy. ... 

There is a downside to this abundance of iron in the general food supply. Well over a million Americans suffer from an inherited genetic disorder called hemochromatosis, or iron overload disease. Such individuals accumulate excess iron in their bodies. The excess iron causes damage to major organs such as the liver, pancreas, and heart. The disease most often affects men between the ages of 30 and 50. Women with the disorder are often protected from developing all the complications of the disease because of their natural loss of iron through menstruation. However, they do develop some of the complications. 

Juvenile hemochromatosis (HH type 2) has clinical features similar to those of type 1, but the clinical course is more severe and characterized by an earlier onset (below 30 years of age). It presents with abdominal pain in the 1 decade of life, and later with cardiac symptoms and endocrine dysfunction. This autosomal recessive disease is rare. The gene has been localised to chromosome Iq and is genetically distinct from HH type 1 [24]. 

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