Genetic or hereditary haemochromatosis is a common inherited disorder of iron overload caused by excess absorption of dietary iron. In Northern Europe 95% of genetic haemochromatosis is caused by two common variants in the HFE gene, C282Y and H63D.
1 in 10 healthy people are heterozygous carriers of a single C282Y or H63D variant.
1 in 200 of the population are homozygous for the C282Y . This genotype confers the highest risk of developing iron overload.
Less commonly, clinical signs of iron overload can be seen in people who have one copy each of the C282Y and H63D variants (so called compound heterozygotes). It is important to recognise that not everyone who inherits two HFE gene variants will develop iron overload which requires treatment. Even fewer will develop the clinical symptoms and signs of genetic haemochromatosis.
Eligibility for genetic testing
- Individuals with biochemical evidence of iron overload (high fasting transferrin and high ferritin levels)
- First degree relatives of individuals who are affected by genetic haemochromatosis
- First degree relatives of individuals found to have a high risk genotype following genetic testing (C282Y homozygotes or C282Y/H63D compound heterozygotes).
Please note:
- Genetic testing for HFE gene haemochromatosis is not indicated for healthy children because it is an adult onset condition.
Further information about HFE haemochromatosis is outlined in the UK guideline below. It should be noted that other, rare, genetic causes of genetic haemochromatosis exist and that secondary iron overload is seen in a variety of conditions including alcoholic liver disease, cirrhosis from any cause, haemolytic anaemia, and transfusional/parenteral iron overload.
UK Guideline
How to test
Genetic testing for genetic haemochromatosis can be requested by the following specialities (see R95 in the National Genomic Test Directory)
- General Practice
- Haematology
- Hepatology
- Cardiology
A 2 - 5ml blood in EDTA (anticoagulant) tube should be sent sent with a completed rare disease test order form to the East Genomics laboratory via your local hospital pathology department.
The clinical indication code 'R95 Iron overload - hereditary haemochromatosis testing' should be recorded on the form. Please include reasons for testing or name of affected relative on sample referral form where applicable.
Please use the East Genomics Laboratory rare disease test order form below: