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Primary Care

Presentation: Patient with a family history of hereditary haemochromatosis

Hereditary haemochromatosis (also known as haemochromatosis) is a genetic condition in which iron may build up in the body, causing multi-organ damage. Genomic testing is recommended in first-degree relatives of individuals who have inherited two copies of the C282Y variant.

At a glance:

  • Hereditary haemochromatosis (HH) is an autosomal recessive genetic condition that leads to a build-up of iron in the body.
  • Iron overload leads to multi-organ damage (in particular, liver, pancreas and joints).
  • Biochemical and clinical expression is seen later in life more in women than in men.
  • HH is one of the most common genetic conditions in people of European descent, with the highest prevalence in Ireland and Britain.
  • Genomic testing is only useful in in first-degree relatives of individuals who have inherited two copies of the C282Y variant.
  • Alert! Diagnosis of HH prior to iron overload allows earlier treatment, reduces complications and improves prognosis.

Example clinical scenario

A 34-year-old lady presents after her brother was given a diagnosis of HH. She is requesting a test for the condition and also asking whether her children can be tested.

Identifying those at risk of a genomic condition

  • HH is an autosomal recessive condition caused by pathogenic variants in the HFE gene leading to excessive absorption of iron.
  • There are two common variants described: C282Y and H63D.
  • Most patients with haemochromatosis have the C282Y variant, with a high carrier frequency in White Northern European populations and especially in those with Celtic heritage.
  • Haemochromatosis due to C282Y homozygosity (where the individual has inherited two copies of C282Y) has variable biochemical penetrance and clinical expression; presentation may be with non-specific symptoms.
  • Compound heterozygosity (where the individual has inherited different HH variants, including with C282Y and H63D) is considered insufficient in itself to cause severe iron overload in the absence of acquired risk factors, such as excess alcohol consumption.
  • In the UK population, 1 in 156 are estimated to be homozygous for C282Y variants.
    • 1 in 5 men and 1 in 10 women who are homozygous for C282Y develop one or more manifestations of haemochromatosis, such as liver disease, diabetes mellitus, rheumatoid arthritis or osteoarthritis.
  • Testing of family members should only be offered to first-degree relatives (parents, siblings and children once they reach adulthood).
  • Testing of family members is only useful if the affected individual is C282Y homozygous. For other genotypes (such as C282Y/H63D compound heterozygotes), if family or cascade screening is indicated, this should be done using biochemical measures of iron overload.

What should you do next?

  • Ask if the presenting individual has any further information regarding the family member’s genomic test result: it is helpful to know if they are homozygous for C282Y.
  • If the family member is C282Y homozygous, offer HFE testing to the presenting individual within primary care. Genomic testing for haemochromatosis can easily be carried out in the primary care setting, see:
  • Organise blood tests for full blood count, liver biochemistry (liver function tests) and iron studies (iron, ferritin and transferrin saturation).
  • Give lifestyle advice, including keeping alcohol intake within recommended limits.
  • HH rarely affects children, so testing can be offered once they reach adulthood and have capacity to consent to testing.
  • If you are discussing genomics concepts with your patients, you may find it helpful to use the visual communication aids for genomics conversations.

Resources

For clinicians

References:

For patients

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  • Last reviewed: 14/01/2026
  • Next review due: 14/01/2028
  • Authors: Dr Jude Hayward
  • Reviewers: Prof Guruprasad P Aithal, Dr Amy Frost, Dr Johanna Wong

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