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- Early clinical features include arthralgia, fatigue, and decreased libido.
- Late effects include cirrhosis of the liver, diabetes, hypermelanotic pigmentation of the skin, and heart failure.
- Because there is no mechanism to excrete excess iron, the excess is stored in muscle and in organs, including the liver, pancreas, and heart, eventually resulting in severe damage to the affected organs.
- Liver damage ultimately may result in hepatocellular carcinoma.
- System(s) affected: Endocrine/Metabolic
- Synonym(s): Bronze diabetes; Troisier-Hanot-Chauffard syndrome
- Predominant age: Metabolic abnormality is congenital, but symptoms usually present in the 5th and 6th decades.
- Predominant sex: Gene frequency: Male = Female (8:1), although clinical signs are more frequent in men (3)
- 3/1,000 people (heterozygote frequency, 1/10) (4)
- The most common genetic abnormality in the US.
Rarely, iron overload may occur as early as 2 years of age. The disorder can be diagnosed before iron overload is clinically apparent.
- The disease is a genetic disorder.
- Affected individuals should not ingest iron supplements, eat raw shellfish, or eat large quantities of iron-rich food, such as red meat.
- Alcohol increases the absorption of iron. (As many as 41% of patients with symptomatic disease are alcoholic.)
- Loss of blood, such as that which occurs during menstruation and pregnancy, delays the onset of symptoms.
- Genetically heterogeneous disorder of iron overload; types 1, 2, and 3 are autosomal recessive; type 4 is autosomal dominant. Neonatal hemochromatosis is rare.
- Penetrance is incomplete; expressivity is variable.
- Factors contributing to variable expressivity include different mutations in the same gene, mitigating or exacerbating genes, and environmental factors.
- Type 1 hemochromatosis is caused by mutations in the HFE gene; type 2 by mutations in either the HFE2 gene or HAMP gene; type 3 by mutations in the TFR2 gene; and type 4 by mutations in the SLC40A1 gene. The cause of neonatal hemochromatosis is unknown.
- The mechanism for increased iron absorption in the face of excessive iron stores is not clear. Iron metabolism appears normal in this disease except for a higher level of circulating iron.
- Iron overload may be caused by thalassemia, sideroblastic anemia, liver disease, excess iron intake, or chronic transfusion.
Commonly Associated Conditions