Hemochromatosis

Risk factors

The main risk factors associated with hereditary hemochromatosis are:

• Genetics: Hereditary hemochromatosis shows an autosomal recessive pattern of inheritance. This means that an individual with the disease must have inherited a mutated and non-functional copy of the HFE gene from both parents. Such an individual is said to be homozygous for mutated copies of the HFE gene. In populations of northern European descent, one in 200-250 are homozygous (have two mutated copies) for C282Y. One in 50 are compound heterozygotes (have one C282Y mutation and one H63D mutation). One in 8-10 are heterozygotes for C282Y (carriers of the mutation). Although two copies of the mutated HFE gene are required to have the disease, not everyone who has two copies actually gets the disorder, meaning in genetic terms, that the genetic variants do not have full penetrance . Most studies report that 60-95% of C282Y homozygotes show symptoms of the disease.
• Ancestry: Hereditary hemochromatosis is found almost exclusively in individuals of northern European ancestry.
• Age: Older people are more likely to develop the disease than younger people. Symptoms do not usually appear in men until after the age of 40. In women, symptoms usually do not appear until after the age of 50 (i.e. after menopause). Individuals carrying two mutated and non-functional copies of the HFE gene rarely develop hereditary hemochromatosis as young children.
• Other factors: The severity of the disorder varies between individuals homozygous for mutated HFE gene copies. Some people may never have symptoms or complications of the disorder while others can be severely affected. Certain factors, including both lifestyle and genetic factors, seem to affect the symptoms and progress of the disorder for those who have inherited mutated copies of the gene:
  • Other genes, besides the hemochromatosis gene, may modify the severity of the disease,
  • Vitamin C in the diet can increase the amount of iron the body absorbs from food and make hemochromatosis worse,
  • Alcohol use can increase the risk of liver damage and cirrhosis,
  • Certain other conditions, such as hepatitis (inflammation of the liver), can increase the effects of iron overload on damage to the liver.

Prevention

The key to preventing hemochromatosis is early diagnosis and treatment. Diagnosis of hereditary hemochromatosis is typically based on blood tests that measure transferrin, iron saturation and serum ferritin concentration, but also on molecular genetic testing for the C282Y and H63D mutations in the HFE gene. Due to incomplete penetrance, the genotype provided by the deCODEme Genetic Scan is in itself insufficient for the diagnosis of hereditary hemochromatosis, but should be considered as evidence of susceptibility to developing the disease. Individuals identified as C282Y homozygotes or C282Y/H63D compound heterozygotes should undergo further testing to identify or exclude iron overload.

As previously described, not everyone who inherits the hemochromatosis mutations develops the disease. For those who have confirmed iron overload, physicians may recommend preventive measures such as dietary changes aimed at reducing iron absorption, for example avoiding taking in extra iron (for example in multivitamins), limiting intake of vitamin C (as it increases iron absorption) and limiting alcohol intake to reduce risk of liver disease.

In terms of treatment, hereditary hemochromatosis is actually one of the few genetic disorders for which there is a relatively simple and effective therapy; iron levels are lowered simply by removing blood (a procedure called phlebotomy ).

When phlebotomy is started early in the course of the illness, it can prevent most of the complications associated with the disease. However, even if phlebotomy is started after complications have occurred, the treatment can still decrease symptoms and improve life expectancy.

More information

You can find out more information about hereditary hemochromatosis by talking to your doctor and visiting these Web sites:

• Centers for Disease Control and Prevention on Iron Overload and Hemochromatosis
• Iron Disorders Institute
• National Heart, Blood, and Lung Institute (NHBLI) article on Hereditary Hemochromatosis
• National Human Genome Research Institute on Hereditary Hemochromatosis
• MedlinePlus article on Hereditary Hemochromatosis

Scientific references

1. Adams, P.C., Reboussin, D.M., Barton, J.C., McLaren, C.E., Eckfeldt, J.H., McLaren, G.D., Dawkins, F.W., Acton, R.T., Harris, E.L., Gordeuk, V.R., Leiendecker-Foster, C., Speechley, M., Snively, B.M., Holup, J.L., Thomson, E., & Sholinsky, P; Hemochromatosis and Iron Overload Screening (HEIRS) Study Research Investigators. . Hemochromatosis and iron-overload screening in a racially diverse population. The New England Journal of Medicine, 325(17), 1769-1778.
2. Cullen, L.M., Gao, X., Easteal, S.& Jazwinska, E.C. . The hemochromatosis 845 GrA and 187 CrG mutations: prevalence in non-caucasian populations. The American Journal of Human Genetics, 62, 1403-1407.
3. Cullen, L.M., Anderson, G.J., Ramm, G.A., Jazwinska, E.C., & Powell, L.W. . Genetics of hemochromatosis.Annual Review of Medicine, 50, 87-90.
4. Lucotte, G. & Dieterlen, F. . A european allele map of the C282Y mutation of hemochromatosis: celtic versus viking origin of the mutation? Blood Cells, Molecules & Diseases, 31, 262-267.
5. Steinberg, K.K., Cogswell, M.E., Chang, J.C., Caudill, S.P., McQuillan, G.M., Bowman, B.A., Grummer-Strawn, L.M., Sampson, E.J., Khoury,M.J., & Gallagher, M.L. . Prevalence of C282Y and H63D mutations in the hemochromatosis (HFE) gene in the United States. JAMA, 285(17), 2216-2222.

This content was last reviewed on February 11, 2010.