[1] The primary mechanism of organ damage is oxidative stress, as elevated intracellular iron levels increase free radical formation via the Fenton reaction.
People with iron overload classically present with the triad of liver cirrhosis, secondary diabetes mellitus, and bronze skin.
Hereditary hemochromatosis is an autosomal recessive disorder with estimated prevalence in the population of 1 in 200 among patients with European ancestry, with lower incidence in other ethnic groups.
[1][7] Non-HFE hereditary hemochromatosis involves mutations in genes coding for the iron regulatory proteins hemojuvelin, transferrin receptor-2 and ferroportin.
Because of the severe sequelae of this disorder if left untreated, and recognizing that treatment is relatively simple, early diagnosis before symptoms or signs appear is important.
[15][16] In general, the term hemosiderosis is used to indicate the pathological effect of iron accumulation in any given organ, which mainly occurs in the form of the iron-storage complex hemosiderin.
), English, and Scandinavian origin[26] have a particularly high incidence, with about 10% being carriers of the principal genetic variant, the C282Y mutation on the HFE gene, and 1% having the condition.
Serum ferritin testing is a low-cost, readily available, and minimally invasive method for assessing body iron stores.
[7] Transferrin saturation of greater than 45% combined with an elevated ferritin level is highly sensitive in diagnosing HFE hemochromatosis.
[39][15] The presence of HFE gene mutations in addition to iron overload confirms the clinical diagnosis of hereditary hemochromatosis.
[citation needed] Liver biopsy is the removal of small sample in order to be studied and can determine the cause of inflammation or cirrhosis.
[citation needed] Magnetic resonance imaging (MRI) is used as a noninvasive method to estimate iron deposition levels in the liver and heart, which may aid in determining a response to treatment or prognosis.
[42] Routine phlebotomy may reverse liver fibrosis and alleviate some symptoms of hemochromatosis, but chronic arthritis is usually not responsive to treatment.
[citation needed] Two newer iron-chelating drugs that are licensed for use in patients receiving regular blood transfusions to treat thalassaemia (and, thus, who develop iron overload as a result) are deferasirox and deferiprone.
[49][50][51] 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.
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.
Archaeologists studying dental plaque have found evidence of tubers, nuts, plantains, grasses and other foods rich in iron.
In theory, the pressures caused by migrating north would have selected for a gene mutation that promoted greater absorption and storage of iron.
Surveys show a particular distribution pattern with large clusters and frequencies of gene mutations along the western European coastline.
[59] 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.
[60][62] 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.