Hemochromatosis is an inherited condition that causes an accumulation of iron in the body. Hemochromatosis occurs when there is a mutation in the HFE gene. Iron accumulation is not a common ailment; usually caused from either hereditary hemochromatosis or from too many blood transfusions (1). Hereditary hemochromatosis causes the intestines to absorb large amounts of dietary iron. The absorbed iron gets stored in different organs of the body. The gene coding for this disorder lies on chromosome 6 (4).
Effects of Iron Absorption Edit
Hemochromatosis causes the body to absorb large amounts of dietary iron. That iron gets absorbed in different organs; such as the liver, heart, pancreas, and skin (1). Storing large amounts of iron at these sites causes them to malfunction. Excess iron in the pancreas can cause diabetes, which could later progress to kidney failure. Storing too much iron in the liver increases the individual's chances of cirrhosis, which when combined with hemochromatosis, increases the individual's chances of liver cancer. Another serious condition of excess iron absorption lies in the heart; if the iron stores in the heart affect the ability to circulate blood, then the individual's chances of developing arrhythmia's, an irregular heartbeat, increases (2). The risk for a heart attack also increases.
There are 3 symptoms that are most commonly presented together in individuals with hemochromatosis, and they are cirrhosis, bronze skin, and diabetes (1). There are other symptoms that present earlier, but they are very general symptoms and can be indications of other possible diseases. These symptoms are considered to be more common, and include: arthritis, joint pain, fatigue, heart failure, and erectile dysfunction (2). A less common symptom seen in individuals with hemochromatosis is the increase in systemic bacterial infections, not just from any bacteria, but from iron-scavenging bacteria. These bacteria have a siderophore system and require iron, which they cannot make, so they "feed" on the excess iron stores within the body (3).
Gene Placement and SNPs Edit
The gene is located on chromosome 6, at the location 6p21.3 (4). There have been 20 SNP mutations identified in this gene that lead to hemochromatosis. The most common HFE SNP mutation in the population is the C282Y mutation. About one in 200 individuals form European descent has both gene mutations, while one in ten individuals has only one gene mutated, so they are carriers (5). The wild-type gene product is a transferrin receptor, that regulates normal iron uptake in the body (2). Once mutated, however, this receptor causes the body to intake much more iron than is necessary. The mutations seen in this gene are point mutations at specific bases within the sequence (4). Altering one of the bases causes the amino acid sequence to be incorrect, which leads to a misfolded protein. Since this mutation is a loss-of-function mutation, it is considered to be recessive. The gene is also not located on a sex chromosome, so it autosomal (4).
Lessons to Take Away Edit
While having this HFE mutation means that the individual is susceptible to excess iron accumulation, most people who have only one mutated gene do not fully develop hemochromatosis. They do, however, have the possibility of passing this gene onto their offspring, and if their partner has the same mutation, then the couple runs the risk of passing the condition along to their offspring. Since Dr. Burke only has one copy of the mutated gene, he will not develop hemochromatosis and will most likely have regular systemic iron levels. A way to keep this condition in check is to limit the amount of iron in one's diet; if they do not eat an iron-rich diet, then they will not store excess iron (5).
1. Hemachromatosis. Wikipedia
2. Hemachromatosis. OMIM
3. Opportunistic Infections with Iron Overload. Harvard
4. HFE Gene. NIH
5. Hemachromatosis. 23 and Me Overview