What Is Iron Overload Disorder? What Is Hemochromatosis? What Causes Iron Overload Disorder?

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Main Category: Blood / Hematology
Article Date: 07 Oct 2009 - 0:00 PDT

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Hemochromatosis, or iron overload disorder, is a disorder which makes the body absorb excessive amounts of iron from the food and drink we consume. The iron overload gives the skin a bronze color, as well as damaging the liver and other organs. Commonly, if it is allowed to progress, the pancreas becomes damaged and the patient develops diabetes.

The surplus iron is stored in the liver, heart, pancreas and other organs. Other life-threatening conditions caused by hereditary hemochromatosis are cancer and heart disease.

As women regularly lose blood during menstruation, hemochromatosis is less common among females than males. Blood loss means iron loss.

Iron overload disorder can be either:

Passed on genetically; this is known as primary hemochromatosis, hereditary hemochromatosis, or classic hemochromatosis.

The result of some condition, such as chronic liver disease, that causes the body to absorb excessive amounts of iron. This is known as secondary hemochromatosis.

If a patient is diagnosed with hemochromatosis, treatment should start promptly to avoid further iron accumulation in the body.

Patients diagnosed with hemochromatosis are told to avoid iron-rich foods, such as red meat, as well as vitamin-C-rich foods - vitamin C allows the body to absorb more iron.

According to Medilexicon's medical dictionary:

Hemochromatosis is "a disorder of iron metabolism characterized by excessive absorption of ingested iron, saturation of iron-binding protein, and deposition of hemosiderin in tissue, particularly in the liver, pancreas, and skin; cirrhosis of the liver, diabetes (bronze diabetes), bronze pigmentation of the skin, and, eventually heart failure may occur; also can result from administration of large amounts of iron orally, by injection, or in forms of blood transfusion therapy."

Classic Hemochromatosis is "a specific inherited metabolic defect [MIM*235200] that increases absorption and accumulation of iron on a normal diet. It is inherited as autosomal recessive and is caused by a mutation in the gene HFE on chromosome 6p21.3"

What are the risk factors for iron overload disorder?

A risk factor is something which increases an individual's chances of developing a disease or condition. For example, smoking raises the risk of developing lung cancer; therefore, smoking is a risk factor for lung cancer.

The known risk factors for hemochromatosis are:

• Possessing two copies of a mutated HFE gene - the greatest risk factor for hereditary hemochromatosis. The person inherits one copy of the mutated HFE gene from each parent.


• Family history - anybody who has a close relative (parent, offspring, brother or sister) with hemochromatosis is significantly more likely to develop it compared to other people.


• Ancestry - people of British, Scandinavian Dutch, German, Irish and French ancestry have a higher risk of developing hemochromatosis compared to others. Their risk of having the HFE gene mutation is greater.


• Gender - men are significantly more likely to develop hemochromatosis compared to women. Signs and symptoms tend to appear earlier on in life in males than females. This is because women lose iron during menstruation and pregnancy. A woman's risk increases after the menopause or a hysterectomy. The male-to-female ratio is 1.8:1 (out of every 28 people with hemochromatosis, 18 are male and 10 are female).

What are the causes of hemochromatosis?

Most of us absorb approximately 10% of the iron we consume. When we have sufficient stores of iron the body reduces the amount of iron absorbed by the intestine to prevent levels from going too high.

People with hereditary hemochromatosis may absorb up to 30% of the iron they consume. With this rate of intake the body cannot get rid of the excessive iron fast enough, so it builds up. The body stores the excess in the tissues of our major organs, mainly in the liver, as well as the heart and pancreas.

People with hemochromatosis may eventually have built up 5 to 20 times the amount of iron they should have. Over time the excess iron can destroy several organs, resulting in organ failure and chronic diseases, such as cirrhosis, heart disease and diabetes.

• Primary hemochromatosis - a genetic mutation Every living organism has genes. Genes are a set of instructions that decide what the organism is like, how it survives, and how it behaves in its environment. A mutation in one gene can significantly change the way our body works.
  
  HFE is the gene that controls the amount of iron we absorb (H = high, FE means iron). There are two common mutations in the HFE gene - C282Y and H63D. In the USA, for example, most people with inherited hemochromatosis have inherited two C282Y copies - one from the mother and the other from the father.
  
  If you have inherited just one gene with the C282Y mutation you are not likely to develop iron overload syndrome, although you will probably absorb more iron than normal. However, you will be a carrier. Approximately 10% of all Caucasians carry one hemochromatosis gene.
  
  If both your parents are carriers you have a 1 in 4 chance of inheriting two mutated genes - one from each parent. However, some people with two copies of the C2H2Y mutation never experience symptoms.
  
  Some individuals may inherit one C282Y and one H63D mutation. A small proportion of these people will develop hemochromatosis symptoms.
  
  Inheriting two copies of H63D is very rare, but it does happen. Some say people with two copies of the H63D mutation are at risk of developing hemochromatosis, while others disagree.


• Secondary hemochromatosis
  
  This type of hemochromatosis occurs as a result of another condition or circumstance (the patient does not have C282Y or H63D mutations). Examples include:
  
  
  • A blood disorder, such as thalassemia.
  
  
  • Chronic liver disease, such as chronic hepatitis C infection, alcoholic liver disease, or non-alcoholic steatohepatitis.
  
  
  • Some types of anemia which require blood transfusion.
  
  
  • Rare inherited diseases that affect red blood cells, including atransferrinemia or aceruloplasminaemia.
  
  
  • Drinking beer that has been brewed in iron containers (African iron overload).
  
  
  • Blood transfusions.
  
  
  • Oral iron pills or iron injections, with or without very high vitamin C intake.
  
  
  • Long-term kidney dialysis.


• Juvenile hemochromatosis
  
  In juvenile hemochromatosis iron build up starts much earlier in life and symptoms appear between 25 and 30 years of age. The patient may develop diabetes and have problems with sexual development. Left untreated juvenile hemochromatosis can be fatal. Juvenile hemochromatosis is an inherited disease caused by a mutation in a gene called hemojuvelin (the HFE gene is not involved).


• Neonatal hemochromatosis
  
  Iron accumulates in the infant's liver so fast that he/she is either stillborn or dies not long after birth. Experts are not sure what the causes of neonatal hemochromatosis are.

What are the signs and symptoms of hemochromatosis?

A symptom is something the patient feels or reports, while a sign is something other people, including a doctor, may detect. For example, a headache may be a symptom while a rash may be a sign.

As signs and symptoms may be mild and could also be indications of other illnesses and conditions, identifying hemochromatosis is often not straightforward.

The main symptoms include:

• Abdominal pain
• Females may stop menstruating
• High blood sugar levels
• Hypothyroidism (low thyroid function)
• Loss of libido (sex drive) and male impotence
• Pain in the joints
• Reduction in size of testicles
• Skin becomes bronzed (has a tanned look)
• Tiredness (fatigue)
• Weakness
• Weight loss

As the disorder progresses, the following conditions may develop:

• Arthritis
• Cirrhosis of the liver
• Diabetes
• Enlargement of the liver
• Heart disease
• Pancreatitis

How is hemochromatosis diagnosed?

As many of the signs and symptoms can exist in other illnesses or conditions which are much more common, hemochromatosis can be difficult to diagnose. Some GPs (general practitioners, primary care physicians) may not have come across it before.

Depending on symptoms, a GP will refer the patient to a hepatologist (a liver specialist doctor) or cardiologist (heart specialist doctor). A specialist will be able to diagnose hemochromatosis.

• Blood tests - two blood tests can detect iron overload, even before symptoms appear.
  
  
  • Serum transferring saturation - transferrin is a protein that carries iron in the blood. This test measures the amount of iron bound to transferrin. Saturation values over 45% are excessively high.
  
  
  • Serum ferritin - this blood test measures the amount of iron the body has stored. If serum transferrin levels are too high the doctor will measure serum ferritin levels.
    
    In order to diagnose hemochromatosis both tests are needed - sometimes they need to be repeated for better accuracy. This is because several other diseases and conditions can raise ferritin levels.
    
    These two blood tests are not usually performed routinely. People who have a parent, child or sibling with hemochromatosis are advised to have these tests, as are people with any of the following signs and symptoms:
    
    
    Diabetes
    Elevated liver enzymes
    Erectile dysfunction (male impotence)
    Extreme tiredness
    Heart disease
    Joint disease
    

People who abuse alcohol, have had many blood transfusions, or have had hepatitis C may have blood tests that suggest iron overload. To confirm a diagnosis of hereditary hemochromatosis, the following additional tests may be ordered:


• Genetic testing - the test will determine whether the patient carries the HFE gene.


• Liver biopsy - the doctor removes a sample of liver tissue with a needle. It is sent to the laboratory to determine what the levels of iron are, whether there is any scarring, cirrhosis or other liver damage.

What is the treatment for hemochromatosis?

• Venesection (phlebotomy) - iron-rich blood is removed from the body regularly, just as if the patient were donating blood. In this case the aim is to bring iron levels down to normal. How much blood is taken and how often depends on the patient's age, overall health and the severity of the iron overload. In most cases blood is removed weekly until levels are back to normal.
  
  When iron levels build up again the patient will need venesection treatment again.
  
  Although venesection cannot reverse the symptoms of cirrhosis, it can improve symptoms such as nausea, abdominal pain and fatigue.


• Medication - the patient may be given a drug that binds iron, which is then excreted from the body.

If hemochromatosis is diagnosed and treated early, before too much excessive iron accumulates, the patient should have a normal lifespan, experts say.

What are the possible complications of iron overload?

If hemochromatosis is left untreated there can be a number of complications, including:

• Cirrhosis - permanent scarring of the liver, which can lead to serious and life-threatening complications.


• Liver cancer - individuals with both cirrhosis and hemochromatosis have a significantly higher risk of developing liver cancer compared to others.


• Diabetes - diabetes can lead to serious complications, such as kidney failure, blindness, and heart problems.


• Congestive heart failure - if too much iron builds up in the heart the body may fail to circulate enough blood to meet its needs. Congestive heart failure is a life-threatening disease if left untreated.


• Irregular heart rhythms (arrhythmias) - the patient may experience chest pain, palpitations and dizziness.


• Skin color - the individual's skin can take on a bronze or gray color because of the deposits of iron in skin cells.

Written by Christian Nordqvist
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today