Might It Be Haemochromatosis?

In the UK, about 250,000 people have a genetic predisposition to haemochromatosis (GH). Only some 5,000 are currently diagnosed but there is evidence that several times that number have tissue damage and disease caused by iron overload. This note is designed to assist GPs in making an early diagnosis of haemochromatosis.

Haemochromatosis is a genetic iron overload disorder. Iron may accumulate from the early twenties onwards, usually later in women. Excess iron is deposited in the liver, as well as the pancreas, other endocrine glands and the heart. Untreated, it may result in irreparable organ damage, including cirrhosis of the liver, late onset diabetes or cardiomyopathy. There may be heavy overload before any symptoms appear. There is strong evidence that early treatment, normally by venesection, preserves normal life expectancy.

Symptoms

Iron overload can give rise to a wide range of non-specific symptoms and clinical findings. Individuals of European origin presenting with any of the following conditions, and particularly a combination of two or more of the following conditions -

•  unexplained weakness or fatigue

•  bronze skin pigmentation

•  abnormal liver function

•  arthralgia/arthritis

•  diminished sex drive or impotence

•  diabetes

•  abnormal heart rhythms

should be considered for investigation for possible iron overload, which would suggest GH (particularly for individuals aged under 50). Arthritis, particularly if it occurs initially in the first and second knuckles, is highly suggestive of GH.

Action

Test such individuals for iron overload by measuring transferrin saturation (in some hospitals a "transferrin index" is calculated). A transferrin saturation >50% (or a raised transferrin index) indicates a risk of iron accumulation, and the patient should be referred to secondary care for further tests. It is important to discuss with any patient diagnosed with GH the desirability of genetic testing for other members of the family. There is at least a 1 in 4 chance that a sibling will have GH. Family checks frequently lead to detection of GH before organ damage has occurred.

Additional information

Among people of Northern European descent GH is the predominant cause of iron overload.

It is an autosomal recessive condition. Some 95% of patients in the UK, with a genetic iron overload, are homozygous for the HFE C282Y gene mutation. In the general population 1 in 200 people have this genotype. Of these most accumulate iron but only a minority will go on to develop clinical symptoms. Additional causative agents seem to be involved but have not yet been clearly demonstrated.

A raised transferrin saturation is an early indication of a risk of iron accumulation.

A raised serum ferritin will confirm increased iron stores but ferritin may be elevated in many other conditions.

The guidance in this note has been endorsed by the medical and scientific advisors to the Haemochromatosis Society.

Detailed recommendations by the British Society for Haematology on the diagnosis and treatment of haemochromatosis are at www.bcshguidelines.org