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Hemochromatosis DNA Test


Find out if you carry the genes which put you at risk of developing Hereditary Hemochromatosis.



What is Hemochromatosis?

Hemochromatosis is a hereditary disease that is caused by increased absorption and storage of iron from food. Excess iron is stored in the body’s joints and organs, eventually leading to serious damage and irreversible diseases, like arthritis, liver disease, heart disease and diabetes, later in life.

Iron is an essential nutrient. We need it to make hemoglobin, a component of blood that carries oxygen from the lungs to all the other parts of the body. However, people with hemochromatosis absorb too much iron from food – 30% compared to the 10% that is normally absorbed. This excess iron cannot be excreted so it accumulates in organs and tissues, leading to serious health complications.

What Causes Hemochromatosis?

Genetic changes in the HFE gene are associated with hereditary hemochromatosis. The HFE protein helps regulate the amount of iron absorbed from our diet, and changes in the HFE gene increase iron absorption leading to excess iron in tissues and organs. There are several other rare forms of hemochromatosis caused by genetic changes in genes other than HFE. This article focuses only on the most common form, known as hereditary or Type 1 hemochromatosis, caused by changes in the HFE gene.

How is Hemochromatosis Inherited?  

The HFE gene is located on Chromosome 6 and we inherit two copies of the HFE gene – one from each parent. Hereditary hemochromatosis occurs when two defective copies of the HFE gene are inherited. Most people with one normal copy and one defective copy do not develop symptoms of the disease, because the normal gene will counteract the defective gene. However, in a small fraction of individuals with only one defective copy, iron overload can be triggered by other factors, such as hepatitis or alcohol abuse.

How Common is Hemochromatosis?

Hemochromatosis is the most common genetic disorder for individuals of European descent. About 1 in 9 individuals of European ancestry carry at least one defective copy of HFE. Approximately 1 in 200 individuals of European ancestry carry two defective copies of HFE and develop hemochromatosis. People with Northern European descent, such as British, Scottish, Irish, Dutch, Danish, Scandinavian, German, French, Spanish and Italian are most at risk for developing hemochromatosis. While both men and women can inherit the defective gene, men are more likely to be diagnosed. On average, men develop symptoms between the ages of 30-50, compared to women who are diagnosed after 50, often 10-15 years after menopause.

Symptoms of Hemochromatosis  

Hemochromatosis is hard to diagnose, because it involves symptoms also seen in many other health conditions. Symptoms vary between individuals and usually only appear later in life.

The early symptoms of hemochromatosis include:

  • Joint pain – in hands, hips, knees and/or ankles (one of the earliest symptoms)
  • Chronic fatigue (one of the earliest symptoms)
  • Lack of energy
  • Weakness
  • Abdominal pain
  • Loss of sex drive
  • Heart problems (heart flutters, irregular heart beat)
  • General darkening of skin color (bronzing)
  • Lack of normal menstruation
  • High blood sugar levels
  • Low thyroid function
  • Abnormal liver function test
  • Depression
  • Shortness of breath

If not detected and treated, hemochromatosis will lead to serious conditions including:

  • Osteoarthritis and osteoporosis
  • Liver disease including enlarged liver, cirrhosis, cancer and liver failure
  • Diabetes
  • Heart problems (irregular heartbeat, heart attack or congestive heart failure)
  • Impotence
  • Infertility
  • Loss of period or early menopause
  • Thyroid deficiency (also can cause depression)
  • Damage to the adrenal glands

DNA Testing for Hemochromatosis

A simple DNA test can be taken to find out whether a person is at risk of developing hemochromatosis. The DNA test identifies three specific changes in the HFE gene, which are associated with an increased risk of hemochromatosis. C282Y (845G>A) is the most common mutation causing hemochromatosis and is associated with the most severe symptoms. H63D (187C>G) and S65C (193A>T) are two other mutations that occur in the HFE gene and can increase the risk of hemochromatosis, however often other precipitating factors (e.g. hepatitis or alcohol abuse) are also required before iron overload occurs. 

To be at an increased risk of hemochromatosis, two defective copies of the HFE gene need to be inherited. Carriers, who have one normal and one defective HFE gene, are generally unaffected, but some do experience slightly increased iron absorption. The most at-risk genotype is two copies of the C282Y mutation (C282Y homozygote). This occurs in 80-85% of affected individuals. Two copies of either of the other two mutations (H63D or S65C) may slightly increase the risk of hemochromatosis, but often no symptoms are observed. Compound heterozygotes have two defective HFE genes, but each copy carries a different mutation. The C282Y/H63D and C282Y/S65C compound heterozygotes are associated with a milder form of hemochromatosis. The H63D/S65C compound heterozygote does not appear to increase the risk of hemochromatosis.

Recommended Links:
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 et al. (2001). Genetics of Iron Storage and Hemochromatosis. Drug Metab Dispos. 29(4): 495-499.

Ajioka RS & Kushner JP (2003). Clinical consequences of iron overload in hemochromatosis homozygotes. Blood. 101(9): 3351-3353.