Haemochromatosis

Hereditary haemochromatosis is a common inherited disorder in which excessive iron absorption may lead to increased body iron stores with deposition of iron in parenchymal cells of the liver, heart, pancreas and other organ.

Disorder other than hereditary haemochromatosis which give rise to iron overload are classified under the broad heading of secondary iron overload syndrome.

Genetics of hereditary haemochromatosis:
Significant iron overloading occurs principally in C282Y homozyotes and occassionally in C282Y/H63D compound heterozygotes. Other HFE genotypes including heterozygosity for C282Y, usually do not develop significant iron overload.

Screening and Diagnosis:
The approach to testing for haemochromatosis may be summarised as follows:
1. In people without family history of HFE

• The transferrin satuation and serum ferritin concentration are the most useful screening tests. The transferrin saturation is more sensitive in detecting early iron overload.
• These tests should be done in the morning after an overnight fast.
• If the fasting transferrin saturation is greater than 45%, the measurement should be repeated and if it remains elevated the HFE gene test should be performed. The ferritin level may also be elevated in patients with haemochromatosis but there are many other causes of elevated ferritin.

2. All first degree relatives of the index case should be screened by testing for mutation in HFE gene. It has been recommended that genetic testing for HFE within families occur during adolescence.

3. Since the discovery of HFE gene, liver biopsy is no longer necessary to diagnose HFE. However, liver biopsy is necessary to establish the presence of cirrhosis and should be considered when there is a history of significant alcohol intake, hepatomegaly on clinical examination, liver enzymes are raised or the serum ferritin is more than 1000 ug/L.

Treatment: consists of life long venesection therapy.

The initial course is one or two venesectin per week until the excess iron stores are removed. Once this is achieved patients usually require one venesection every 3-4 months to keep iron stores at low normal levels.

However, patients with severe cardiac disease may not tolerate venesection and these patients may be given iron chelation therapy with desferrioxamine.

It is the usual practice that cirrhotic patient should undergo HCC surveillance every six months with hepatic USS and serum alpha-fetoprotein measurement.