Haemochromatosis



Last Review Date: June 8, 2019


Overview

Haemochromatosis is defined as iron overload leading to end organ damage. As the body does not have a way to excrete excess iron, there is a progressive build-up of iron in tissues and organs. The excess iron is stored in your organs, especially the liver, heart and pancreas. This can lead to organ dysfunction and failure. As it progresses, complications can include arthritis, diabetes, liver cirrhosis, heart arrhythmias and failure, loss of libido and a charateristic metallic grey pigmentation of the skin.

This condition may be inherited which is called hereditary haemochromatosis (HH) or acquired, which is caused by some other disease or underlying condition. The most common form is an inherited disorder.
 

Hereditary haemochromatosis (HH)
This is seen mainly in white skinned people (Caucasians). HH is also the most common genetic disorder in Australia, affecting about one in every 200 Australians of European origin. It causes the body to absorb too much iron resulting in iron overload. 

Iron is absorbed from the diet through the small intestine and the amount absorbed is determined by the body's needs. People with HH absorb more iron than their body needs. As the body does not have a way to increase excretion of the excess iron there is a progressive build-up of the excess iron in tissues and organs. 
Early iron overload might have no symptoms, even though organ damage is occurring. Symptoms tend to occur after the age of 40, but may be earlier or later. Early symptoms may include fatigue, abdominal pain and joint aches
 

The HFE gene
HH is an autosomal recessive disorder. Everyone has two copies of the HFE gene- one inherited from their mother and the other one inherited from their father. HH is usually caued by a mutation in the HFE gene. To have HH a person needs to have a fault in both their HFE genes.

The most common mutation is called C282Y. Other mutations are called H63D ( the second most common) or S65C. Two copies of C282Y or a copy of C282Y together  with a copy of H63D or S65C, places a person at risk for HH. About 1 in 200 Caucasians of Northern European descent have two abnormal (mutated) copies of the gene associated with HH and are at risk for developing iron overload and clinical symptoms. However, not all the people with two copies of the mutated gene develop HH. It is estimated that up to 45% of men and 10% of women who have a double dose of the C282Y gene fault will develop significant problems ushc as liver cirrhosis. Clinical disease is less common in females due to physiological blood loss from menstruation and pregnancy. More than 80% of cases of HH are due to C282Y homozygosity (carrying two copies of the C282Y gene). Around 80% of men and 60% of women with the double dose of the C282Y gene fault will havve raised iron levels in their body. The reason why some have ery high iron levels and severe medical problems whilst others have midler or even no problems, is not yet understood.

In Australia, around 1 in 5 people have a singe copy of the H63D gene fault and 1 in 9 a single C282Y gene fault. People with one abnormal (mutated) copy of the HFE gene, are referred to as carriers. Carriers are not at particular risk for developing iron overload. The carrier status is much lower in other racial/ethnic groups.


Acquired Haemochromatosis
This is due to a variety of  other diseases and conditions. Examples include:
  • Chronic liver disease, such as chronic hepatitis C  infection, alcoholic liver disease, or non-alcholic steatohepatitis (NASH)
  • Alcohol abuse
  • Multiple blood transfusions e.g. for the treatment of thalassaemia
  • Some haemolytic diseases
  • Rarely excessive oral iron supplementation

 


Tests

The tests below are used to detect and diagnose hemochromatosis and evaluate body organs for the severity of iron overload. They may also be used to monitor the effectiveness of treatment.

  1. Iron studies- Serum iron, Total Iron Binding Capacity (TIBC), Ferritin, transferrin saturation. Fasting samples are preferred due to the diurnal variation of circulating iron, unless ferritin level is requested on its own. Ferritin
  2. Liver Function Tests (LFT)- Could become abnormal e.g. elevated ALT and AST
  3. Genetic testing- This is done for HH. Most laboratories test for C282Y mutation and H63D mutation in the HFE genes; See “The HFE Gene”above. This done through a blood test which can be used in identifying family members (For first and second degree relatives of an index case,) at risk. Genetic testing may be used to confirm a diagnosis, but many people who have genetic mutations associated with the disease never develop symptoms.
  4. Liver biopsy and MRI — Assessment of iron overload status has traditionally been undertaken using percutaneous liver biopsy.  But there is a non-invasive reasonably accurate measure of liver iron loading status through magnetic resonance imaging (MRI) of the liver using a newly patented technique called Ferriscan® now. While it is usually not necessary to confirm the diagnosis by examination of a liver biopsy specimen for iron accumulation, a biopsy is often done to help determine the extent of liver damage.

Close family members including parents, siblings and children should be screened for haemochromatosis by measuring the transferrin saturation and serum ferritin, and in some cases by genetic testing.
 


Treatment

The goals of haemochromatosis treatment are to reduce the amount of iron in the body and maintain it at near normal levels, to minimize permanent organ damage, and to address complications. Most importantly, early diagnosis and treatment of HH prevents complications and results in a normal life expectancy. If a person has acquired haemochromatosis, then treatment should also address the underlying disorder or condition. With regards to HH because not all individuals who have the genetic changes need treatment, only those who have organ damage from excess iron are generally identified and treated.

Venesection is a simple and effective way to both prevent and manage the condition. It involves withdrawing a unit of blood at frequent intervals to reduce body iron stores as determined by the ferritin level. The frequency and length of treatment depend on the degree of iron overload. Once iron levels are normalised, units of blood are withdrawn at longer intervals to avoid re-accumulation. The monitoring is particularly done with ferritin. The treatment, which should be life-long, is usually well tolerated.

Someone who has acquired haemochromatosis may not require long-term blood removal treatment if the underlying condition can be resolved--and if their iron overload is due to many transfusions, it may not be possible to do venesection if the need for transfusions is still present. There are also drugs that bind iron and allow it to be eliminated in the urine, (iron chelation drugs) and drugs that reduce gastric acid production (proton pump inhibitors) that reduce the amount of iron in food that is absorbed. These may be used for people who cannot safely have venesection performed.




Treatment of hereditary haemochromatosis consists of withdrawing a unit of blood at frequent intervals to reduce body iron stores as determined by the ferritin level. The frequency and length of treatment depend on the degree of iron overload. Once iron levels are normalised, units of blood are withdrawn at longer intervals to avoid re-accumulation. The treatment, which should be life-long, is usually well tolerated.


Related pages

On this site
Tests: Transferrin saturation, ferritin, iron tests, HFE Mutations  
Conditions: Liver Disease 
Inside the lab: Genetic Testing

Elsewhere on the web
Better Health Channel: Haemochromotosis
Iron Studies Standardised Reporting Protocol- RCPA
Haemochromatosis Society Australia
Haemochromatosis Australia
Hereditary Haemochromatosis Diagnosis and management