are deferasirox and deferiprone. chelating polymers a minimally invasive approach to hereditary hemochromatosis treatment is the maintenance therapy with polymeric chelators. these polymers or particles have a negligible or null systemic biological availability and they are designed to form stable complexes with fe2+ and fe3+ in the git and thus limiting their uptake and long-term accumulation. although this method has only a limited efficacy, unlike small-molecular chelators, the approach has virtually no side effects in sub-chronic studies. interestingly, the simultaneous chelation of fe2+ and fe3+ increases the treatment efficacy. prognosis in general, provided there has been no liver damage, patients should expect a normal life expectancy if adequately treated by venesection. if the serum ferritin is greater than 1000 ug/l at diagnosis there is a risk of liver damage and cirrhosis which may eventually shorten their life. the presence of cirrhosis increases the risk of hepatocellular carcinoma. other risk factors for liver damage in hemochromatosis include alcohol use, diabetes, liver iron levels greater than 2000 μmol/gram and increased aspartate transaminase levels. the risk of death and liver fibrosis are elevated in males with hfe type hemochromatosis but not in females; this is thought to be due to a protective effect of menstruation and pregnancy seen in females as well as possible hormone related differences in iron absorption. epidemiology hhc is most common in certain european populations (such as those of irish or scandinavian descent) and occurs in 0.6% of some unspecified population. men have a 24-fold increased rate of iron-overload disease compared with women. stone age diet and the environment are thought to have had large influence on the mutation of genes related to iron overload. starting during the mesolithic era, communities of people lived in an environment that was fairly sunny, warm and had the dry climates of the middle east. most humans who lived at that time were foragers and their diets consisted largely of wild plants, fish, and game. archaeologists studying dental plaque have found evidence of tubers, nuts, plantains, grasses and other foods rich in iron. over many generations, the human body became well-adapted to a high level of iron content in the diet. neolithic in the neolithic era, significant changes are thought to have occurred in both the environment and diet. some communities of foragers migrated north, leading to changes in lifestyle and environment, with a decrease in temperatures and a change in the landscape which the foragers then needed to adapt to. as people began to develop and advance their tools, they learned new ways of producing food, and farming also slowly developed. these changes would have led to serious stress on the body and a decrease in the consumption of iron-rich foods. this transition is a key factor in the mutation of genes, especially those that regulated dietary iron absorption. iron, which makes up 70% of red blood cell composition, is a critical micronutrient for effective thermoregulation in the body. iron deficiency will lead to a drop in the core temperature. in the chilly and damp environments of northern europe, supplementary iron from food was necessary to keep temperatures regulated, however, without sufficient iron intake the human body would have started to store iron at higher rates than normal. in theory, the pressures caused by migrating north would have selected for a gene mutation that promoted greater absorption and storage of iron. viking hypothesis studies and surveys conducted to determine the frequencies of hemochromatosis help explain how the mutation migrated around the globe. in theory, the disease initially evolved from travelers migrating from the north. surveys show a particular distribution pattern with large clusters and frequencies of gene mutations along the western european coastline. this led the development of the "viking hypothesis". cluster locations and mapped patterns of this mutation correlate closely to the locations of viking settlements in europe established c.700 ad to c.1100 ad. the vikings originally came from norway, sweden and denmark. viking ships made their way along the coastline of europe in search of trade, riches, and land. genetic studies suggest that the extremely high frequency patterns in some european countries are the result of migrations of vikings and later normans, indicating a genetic link between hereditary hemochromatosis and viking ancestry. modern times in 1865, armand trousseau (a french internist) was one of the first to describe many of the symptoms of a diabetic patient with cirrhosis of the liver and bronzed skin color. the term hemochromatosis was first used by german pathologist friedrich daniel von recklinghausen in 1889 when he described an accumulation of iron in body tissues. identification of genetic factors although it was known most of the 20th century that most cases of hemochromatosis were inherited, they were incorrectly assumed to depend on a single gene. in 1935 j.h. sheldon, a british physician, described the link to iron metabolism for the first time as well as demonstrating its hereditary nature. in 1996 felder and colleagues identified the hemochromatosis gene, hfe gene. felder found that the hfe gene has two main mutations, c282y and h63d, which were the main cause of hereditary hemochromatosis. the next year the cdc and the national human genome research institute sponsored an examination of hemochromatosis following the discovery of the hfe gene, which helped lead to the population screenings and estimates that are still being used today.