What is Hemochromatosis?
Hemochromatosis is an iron disorder in which the body absorbs and stores too much iron. There are two types of hemochromatosis – primary and secondary. Secondary hemochromatosis is usually the result of another disease that causes an iron overload. Primary hemochromatosis is a genetic disorder that leads to an excess of iron in the body’s joints and organs, causing serious damage and can be fatal if left untreated. Iron is found in many foods and normally people absorb only about 8-10% of this iron in order to make hemoglobin to carry oxygen in the blood. People who do not have adequate iron in their diet suffer from anemia, while people affected with hemochromatosis can absorb 3 – 4 times more iron than normal. The excess iron cannot be excreted and accumulates in organs and tissues, eventually leading to serious health complications.
What Causes Hemochromatosis?
Hereditary or primary hemochromatosis is caused by defects in the HFE gene. One of the roles of the HFE protein is to regulate the amount of iron that is absorbed from the diet. When mutations occur in the HFE gene, too much iron is absorbed and accumulates in the body.
Genetics of Hemochromatosis
There are three known mutations in the HFE gene that cause excess iron accumulation. These genes are commonly referred to by the amino acid nomenclature and are C282Y (845G>A), H63D (187C>G) and S65C (193A>T). Each person carries two copies of the HFE gene, one inherited from each parent. If a person inherits one normal copy of the HFE gene and one mutated copy, they are known as a heterozygote or carrier and only have a low risk of developing hemochromatosis. Homozygotes have inherited two copies of the HFE that both carry the same genetic mutation and have an increased risk of hemochromatosis. Compound heterozygotes inherit two mutated HFE genes, but each copy has a different genetic mutation. Compound heterozygotes also have an increased risk of hemochromatosis.
What Other Factors Contribute to Hemochromatosis?
The C282Y (845G>A), H63D (187C>G) and S65C (193A>T) mutations in the HFE gene are all known to increase the risk of hemochromatosis. However, not everyone who inherits two copies of these mutations (homozygotes or compound heterozygotes) develops hemochromatosis. This indicates that other factors are also involved. These factors could be other unidentified genetic mutations in the HFE gene or other genes, or environmental factors that cannot be tested for by this genetic analysis.
Other Types of Hemochromatosis
The hemochromatosis described on this website is known as Type 1 or hereditary hemochromatosis. There are also other, less common, forms, which are not caused by mutations in the HFE gene. These include juvenile (type 2) hemochromatosis (caused by a mutation in the HJV gene), neonatal hemochromatosis (unknown cause), TFR2-related hemochromatosis (mutations in the TFR2 gene) and type 4 hemochromatosis (mutations in the SLC40A1 gene). These other forms of hemochromatosis will not be diagnosed by the HFE genetic analysis offered in our laboratory.
Next, Signs and Symptoms of Hemochromatosis »
Duchini A, Klachko DM, Sfeir HE (2014). Hemochromatosis.
Hemochromatosis.org. Provided by Iron Disorders Institute.
Hemochromatosis. National Heart, Lung, and Blood Institute. National Institutes of Health.
Beutler E, Felitti V, Gelbart T, Ho N (2001). Genetics of Iron Storage and Hemochromatosis. Drug Metabolism and Disposition. 29(4): 495-499.