Haemochromatosis

Iron overload may be caused by increased absorption of iron from the intestine, even when the body does not require it. This is called primary iron overload. This is usually caused by an inherited abnormality known as hereditary haemochromatosis.

There are several forms of haemochromatosis. In genetic haemochromatosis, inheritance of a faulty or abnormal gene is responsible for an increase in the amount of iron entering the body.

Haemochromatosis type 1 (also HFE hereditary haemochromatosis) is a hereditary disease characterized by excessive intestinal absorption of dietary iron resulting in a pathological increase in total body iron stores. Humans, like most animals, have no means to excrete excess iron. Excess iron accumulates in tissues and organs disrupting their normal function. The most susceptible organs include the liver, adrenal glands, heart, skin, gonads, joints and pancreas. Patients can present with liver scarring (cirrhosis), joint pains (polyarthropathy), heart failure or diabetes. The hereditary form of the disease is most common among those of Northern European ancestry, in particular those of Celtic descent. The disease is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. People who carry one copy of the mutated gene usually do not show signs and symptoms of the condition.

Hereditary haemochromatosis (HHC) is a group of disorders related to deficiency of the iron regulatory hormone called “hepcidin”. HHC is also an autosomal recessive genetic disease.

Other inherited blood disorders such as thalassemia and sickle cell anaemia can cause iron overload. Here, overload occurs when the body accumulates iron in an attempt to counteract anaemia, and by blood transfusions. Transfusions are often a major part of therapy for these disorders, whether given occasionally during acute crises or as part of a regular treatment programme. People with these diseases cannot be treated in the same way as for genetic haemochromatosis. Instead, they may need regular chelation therapy (the use of drugs which bind with metals in the body so that they can be excreted) and blood exchange rather than transfusions. You can discuss how to prevent iron overload in thalassemia and sickle cell disease with your haematologist.

The excess levels of iron can lead to non-specific symptoms. It is worth noting that more and more people are being diagnosed with hereditary haemochromatosis without showing any symptoms.

Symptoms can be difficult to spot because they’re often mild initially, with many potential causes. Fatigue and lethargy are common, and joint pain or arthritis may occur. Sexual problems, particularly impotence in men or loss of menstruation in women, may be an important early sign.

As the iron overload increases, sufferers may experience the following diseases:

• Liver disease. The liver is the main site of excessive iron build up. The disease causes scarring or liver fibrosis leading to cirrhosis. Symptoms include abdominal pain, jaundice, swelling of the ankles or abdomen and enlargement of the liver or spleen.
• Heart disease. Excess iron deposits may lead to one of two heart conditions: heart failure (indicated by tiredness, lack of energy, shortness of breath and ankle swelling) and abnormal heart rhythms. Patients may experience extra heart beats known as ectopics or disorders where the heart goes either too fast (tachycardia) or too slow (bradycardia).
• Pancreatic disease. Sugar diabetes (diabetes mellitus) may be an early sign of haemochromatosis and develops in up to half of all patients with advanced disease. Diabetes is due to excess iron in the pancreas gland damaging the insulin producing cells. This complication together with the dark skin pigmentation that can occur has led to haemochromatosis sometimes being called ‘bronze diabetes’.
• Rarely, endocrine gland problems particularly with pituitary, thyroid or sex hormones can occur, as can skin and neurological disease.

There are two known common variants in the HFE gene that have been associated with iron overload. These are called C282Y and H63D. The numbers 282 and 63 indicate where the mutations are found on the HFE gene. The mutations occur on a specific chromosome (chromosome six).

The C282Y mutation is the more severe. It is found only among people of northern European origin and may date back several thousand years. The H63D variant is associated with a milder disease and usually only when inherited with a copy of the HFE gene having the C282Y mutation. It is thought to be much older and is spread more widely throughout the world.

Not all people with haemochromatosis will have typical gene mutations. To develop haemochromatosis that is linked to the HFE gene, both copies of the gene must be affected. For this reason it is known as a ‘recessive’ disorder, as opposed to a ‘dominant’ disorder where only one gene is required. In over 90% of people diagnosed with the disorder, both genes have been found to be abnormal. A person who has only one abnormal gene is known as a ‘carrier’. They are not usually affected but can pass on the gene to their own children.

People who inherit the same mutated gene from both of their parents (e.g. C282Y/C282Y) are termed ‘homozygote’. Those who inherit one mutated gene only (carriers) are called ‘heterozygote’. People who have two different forms of the mutated gene are called ‘compound heterozygotes’.

Doctors may be required to investigate and rule out a range of other illnesses that share the same symptoms before haemochromatosis is suspected. Abnormal iron levels are often the only sign of haemochromatosis. Therefore, the most important tests for detecting iron levels in the blood are the transferrin saturation and serum ferritin tests.

Transferrin is a protein that binds iron in the blood serum and carries it around your body. This test measures the level of iron in your blood against the capacity of the blood iron binding protein (transferrin) to bind it. This is known as the Total Iron Binding Capacity or TIBC. The transferrin saturation (TS) is the concentration of serum iron divided by the TIBC expressed as a percentage. A value over 55% in a man and over 50% in a woman may indicate an overload of iron. If this is the result you may be asked to provide another sample after an overnight fast so that a more accurate reading can be gained.

Ferritin is the protein that stores iron in the tissues. Small amounts of ferritin are found in the blood serum. As the amount of iron in your body increases, so do the levels of ferritin in the serum.

Genetic testing is a recent development in haemochromatosis and is used to determine whether you have the HFE gene mutation. Doctors may use the test to identify the cause of high iron levels detected in the TS and SF tests. Your blood cells will be examined for the HFE gene mutations C282Y and H63D by using a simple blood test. If homozygosity for C282Y or compound heterozygosity for C282Y/H63D is found, the test is ‘positive’. Genetic testing is positive in over 90% of people with iron overload.

If liver disease is suspected, liver function tests (LFTs) may also be used. In particular, doctors will be concerned to measure levels of the liver enzymes ALT and AST which are increased during liver inflammation (hepatitis). if you have high serum ferritin (over 1000 mcg per litre) or any sign of liver disease, doctors may use a liver biopsy to confirm their diagnosis and to assess the severity of any liver damage caused by fibrosis/cirrhosis.

Haemochromatosis responds well to treatment, which aims to remove excess iron from the body. The usual treatment is quite simple. Blood is removed from the body on a regular basis – about the same amount taken in a blood donation, around 500ml. This leads to an overall drop in iron levels. For people unable to use phlebotomy for medical reasons, a medication called chelation therapy (you will need to see a haematologist or gastroenterologist for specific advice).

You can make an appointment to see one of our Gastroenterologists by booking online or call our office Rosebud Endoscopy and one of our friendly receptionists will be able to assist you.