Hemochromatosis is the term used to describe a genetic disorder that results in the abnormal accumulation of iron in parenchymal organs, causing varying degrees of organ damage. It is one of the commonest autosomal recessive genetic disorders and is most frequently seen in inhabitants of the northern hemisphere, particularly those of Celtic descent.


hemochromotosis 5.jpg

Sites of iron deposition in hemochromatosis


Hemochromatosis is caused by a defect in the hemochromatosis gene (HFE). There are two forms of this defective gene known as C282Y and H63D which are responsible for most cases of hereditary hemochromatosis. The mechanism by which these defective genes disrupt iron metabolism is not known, however it is thought to be linked to production of hepicidin.

In normal circumstances the intake of iron from the intestine and the consumption and excretion of iron by tissue and organs is controlled by a feedback mechanism that ensures optimum levels of circulating iron. An important constituent of this iron control mechanism is a peptide manufactured in the liver called hepcidin. Hepcidin prevents the release of iron from cells by altering or degrading ferroportin, the protein responsible for transporting iron out of cells. Patients with hemochromatosis have been shown to have low levels of hepcidin. This results in excessive absorption of iron from the intestine and excretion of iron from cells in the liver and intestine causing high blood levels and deposition of toxic levels of iron in a number of organs. The organs most affected are the liver, heart, pancreas, endocrine glands and joints.  Damage to these organs can result in a variety of disease conditions such as cirrhosis, diabetes, heart failure, arthropathy and impotence

The toxic effect of excess iron deposition is thought to be due to free radical formation. The presence of free iron in biological systems can lead to the rapid formation of damaging reactive oxygen metabolites, such as the hydroxyl radical and the superoxide radical. These can produce DNA cleavage, impaired protein synthesis, loss of cell integrity and altered cell proliferation, resulting in cell injury or death.

Although the presence of the HFE gene is strongly associated with hemochromatosis, only 65-75% of these patients will develop symptoms of disease. This indicates that other factors such as diet, environment or lifestyle may be involved in the expression of the gene

The prevalence of hemochromatosis in America, Europe and most western countries is approximately 1 in 300 of the population. One in ten of theses populations are carriers of the defective gene. In Ireland it is estimated that 15% of the population are carriers of a defective gene and at least 2% of the population have hemochromatosis

 Hemochromatosis has a long incubation period and symptoms are not usually seen before 40 years of age in men and 50 years of age in women.

Early symptoms are non specific and include excessive fatigue or lack of energy, joint pain, abdominal pain and impotence. If untreated, the disease may progress to liver disease, diabetes, arthralgia and cardiac disease.

Because the symptoms are non specific and late onset, this condition is often undiagnosed, which is unfortunate as the treatment is simple and effective.

Hemochromatosis is treated by removal of blood at regular intervals, once or twice a week initially and then every two to three months. This removes excess iron which is bound to haemoglobin, and prevents deposition in tissue and organs.

For more information see Hemochromatosis in the Disease Descriptions section

To Screen or Not to Screen

There are currently no major screening programmes for the general population in countries with a significant incidence of hemochromatosis and the US preventive services task Force has recently advised against screening of the general population in the US. This decision was taken on the basis that there was insufficient research to be able to predict the impact or benefit from screening.

Despite this ruling, there are situations in which screening would be beneficial. These include the following.

  • In those cases where a first degree relative has hemochromatosis
  • In those cases where there unexplained elevated serum iron or ferritin in individuals of Northern European or Celtic origin
  • In some cases of unexplained abnormal liver function tests in patients of Northern European or Celtic origin
  • Any combination of the above

Screening of at risk patients is important as consumption of iron rich foods or vitamin supplements can precipitate or aggravate symptoms. Early diagnosis can prevent serious organ damage and prompt screening of at risk relatives.

Patients who have the HFE gene and have biochemistry results consistent with iron overload can be successfully treated by periodic removal of iron rich blood.


DID YOU KNOW – The Liver is the Body’s Main Chemical Factory.

The liver is a triangular shaped four lobed organ weighing approximately 1.5 kg. that is situated in the upper right quadrant of the abdomen. The liver is the largest of the body’s internal organs and is responsible for the manufacture, breakdown and storage of a wide variety of essential chemicals.



The liver, gallbladder, stomach and small intestine


Apart from its function as an foreign particle, toxin and red blood cell filter, the liver also


  • Bile which is essential for neutralisation of stomach acid and digestion of food
  • Glucose from carbohydrates
  • Glycogen from glucose
  • Cholesterol,  triglycerides and apolipoproteins
  • Various proteins including albumin, C-reactive protein, acute phase protein and a number of globulins
  • Most of the factors responsible for bleeding and clotting of blood including coagulation cascade factors, antithrombin, antitypsin, fibronectin, protein C, plasminogen, antiplasmin and complement components
  • Carrier proteins such as ceruloplasma (copper), haptoglobin (haemoglobin), transthyrectin (thyroxine), transferrin (iron) and vitamin D binding protein (vitamin D).
  • Hormones such as insulin -like growth factor, important for childhood growth, and thrombopoietin which regulates the production of blood platelets by the bone marrow
  • Angiotensinogen which is converted to angiotensin a powerful vasoconstrictor.

Breaks Down

  • Various hormones including insulin
  • Haemoglobin to produce bilirubin
  • Ammonia to urea
  • Drugs by methylation. Some of these methylation products are toxic.
  • Ingested toxins


  • Glucose in the form of glycogen
  • Iron and copper
  • Vitamin A
  • Vitamin D
  • Vitamin B12

This is not a complete list but serves to demonstrate the complexity and importance of this often underappreciated organ.


NEWS – More Diseases Linked to Vitamin D Deficiency

The number of disease associated with vitamin D deficiency seems to increase with every passing month. Recent studies at the Wellcome Trust Centre for Human Genetics in Oxford have shown that vitamin D has more than 2,700 binding sites on the human genome. These binding sites control the switching on or off of a wide variety of genes and demonstrate the importance of this vitamin in the control of these switching mechanisms.


newsletter vitamin D 2.jpg

Synthesis of vitamin D


Of particular interest was the high degree of vitamin D binding in genes associated with a number of autoimmune diseases including type 1 diabetes, Crohn’s disease and multiple sclerosis. High binding was also noted in areas of the genome associated with some cancers such as leukaemia and colorectal cancer.

These findings further enhance the proposition that vitamin D deficiency may be a significant risk factor for a number of diseases. Vitamin D deficiency has been linked to osteoporosis, heart disease, hypertension, colon, lung, prostate and breast cancers, type 1 diabetes and multiple sclerosis. Most if not all of these conditions have increased incidence and poorer survival in northern latitudes, when compared with populations at the equator.

Vitamin D is normally produced by the action of sunlight on skin. In northern latitudes where there is limited sunlight, the risk of vitamin D deficiency is high.

Current recommendations suggest that sun exposure of 5-10 minutes for very light skin, 10-15 minutes for light skin, 30-60 minutes for darker skin, for a few days each week will produce  adequate blood levels of vitamin D. If adequate exposure to sunlight is not possible, supplementation with 1000 -4000 IU of vitamin D3 each day is strongly recommended.