Haemochromatosis

What is haemochromatosis?

Haemochromatosis is a genetic iron storage disease in which the body absorbs excessive amounts of iron from the diet. Excess iron is usually metabolised and excreted from the body, but in haemochromatosis, excess iron is deposited in the liver, pancreas, heart, endocrine glands and joints.

Who gets haemochromatosis?

Haemochromatosis is ten times more common in males than in females and usually presents at between 40 and 60 years of age.

What is the cause of haemochromatosis?

Haemochromatosis is caused by mutations in the HFE gene with autosomal recessive inheritance. Two mutations identified in the HFE gene are C282Y and H63D. Haemochromatosis is the most common single-gene inherited disorder in whites, with one in ten persons carrying one abnormal gene.

• For an individual to have haemochromatosis they must have inherited a defective gene from each parent.
• A person who has one defective gene and one normal gene is a carrier and will lead a perfectly healthy life. However, the carrier is able to pass on the defective gene to a son or daughter.
• Up to half of all patients with porphyria cutanea tarda carry at least one HFE gene mutation and this may contribute to the increased stores of liver iron seen in these patients.

What are the signs and symptoms of haemochromatosis?

The four main features characterise haemochromatosis are:

• Cirrhosis of the liver
• Diabetes mellitus
• Increased skin pigmentation
• Heart failure.

How does haemochromatosis affect the skin?

• Increased pigmentation affects more than 90% of patients.
• Skin pigmentation is often one of the first signs of the disease and may precede the other features by many years.
• Hyperpigmentation is most evident on sun-exposed skin, particularly on the face.
• The colour of skin can be slate grey or brownish bronze.
• Ichthyosis-like changes (scaling)
• Skin thinning
• Partial loss of body hair; the pubic region is most affected.
• Koilonychia (thinned spoon-shaped nail), usually of the thumb and index and middle fingers
• Haemochromatosis can be associated with the disease porphyria cutanea tarda (PCT). PCT may cause fragility and blistering of the skin, especially on the backs of the hands.

How does haemochromatosis affect other body organs?

• Enlarged liver occurs in more than 95% of patients and is often accompanied by chronic liver disease (cirrhosis) and liver failure.
• Diabetes mellitus, often requiring insulin therapy, is seen in 30-60% of patients.
• Cardiomyopathy (disease of the heart muscle)
• Loss of sex drive, impotence in men, absent or irregular menstrual periods and early menopause in women
• Arthritis, commonly in the knuckle and first joint of the first two fingers
• General symptoms including chronic fatigue, weakness, lethargy and apathy

Patients with haemochromatosis may develop one or more of the above symptoms over a period of time as iron slowly accumulates and deposits in organs. Often the disease is not diagnosed until routine blood tests show elevated blood iron levels. Patients often seek help because of tiredness, abdominal discomfort, joint pains, and general malaise experienced over a prolonged period of time.

How is the diagnosis of haemochromatosis made?

Several tests can be done to confirm the diagnosis of haemochromatosis.

• Laboratory studies show elevated levels of iron in the blood and body stores. serum iron concentrations greater than 150 mcg/dL and serum ferritin levels > 500 ng/mL.
• 92% of patients with haemochromatosis have transferrin saturation greater than 62%.
• X-rays may show an enlarged heart, and blood tests may show liver disease or diabetes, increased blood vessels in the lungs and restrictive cardiomyopathy on echocardiograms.
• Genetic tests for the C282Y and H63D mutations are widely available. These tests can be performed to confirm the diagnosis or as a screening mechanism for early detection of at-risk individuals.

What is the treatment for haemochromatosis?

Treatment of haemochromatosis consists of regular removal of blood and is similar to making a blood donation (venesection therapy or phlebotomy). Every mL removed contains a 0.5 g of iron. Depending on the amount of iron overload the procedure may initially be performed once weekly or once monthly. This regularity of treatment continues until serum ferritin levels fall back to normal; this may take up to 2 years or more. After this, lifelong maintenance therapy needs to be set in place as excess iron continues to be absorbed. On average venesection is required every 3–4 months to prevent build-up and maintain healthy levels. Regular monitoring of serum ferritin, transferrin saturation, haematocrit and haemoglobin is necessary throughout the treatment process.

It is essential to detect haemochromatosis as early as possible so that venesection can be instituted to prevent the build-up of iron and potential complications. Once complications such as diabetes and cirrhosis have developed, they cannot be reversed. Tiredness and abdominal pain should diminish, and increased pigmentation of the skin should fade over time once treatment has started. Arthritis, however, may fail to improve with venesection.

Haemochromatosis cannot be treated with a low iron diet. However, some foods affect the way the body absorbs iron. The following dietary tips may play a small part in reducing the symptoms of the disease.

• Minimise alcohol intake, particularly with meals – alcohol may lead to increased iron absorption and increase the risk of liver disease.
• Avoid eating offal (liver, kidney etc.) and red meat – iron absorption from red meat is 20–30% compared with 1–20% for vegetables and grains.
• Avoid vitamin supplements or tonics containing iron or vitamin C - vitamin C enhances the absorption of iron from the diet.