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Primary Care

Presentation: Patient with iron overload (suspected hereditary haemochromatosis)

Hereditary haemochromatosis is an inherited condition that leads to an excessive absorption of iron in the body and can cause multiorgan damage.

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 multiorgan damage (in particular, liver, pancreas and bones).
  • HH is one of the most common genetic conditions in northern European – particularly Celtic – populations.
  • Alert! Early symptoms are non-specific.

Example clinical scenario

A 45-year-old man has recently been diagnosed with diabetes mellitus. Prior to diagnosis, he complained of fatigue and joint pains. These symptoms persisted despite adequate management of his diabetes. Blood tests revealed a ferritin level of 1,500 micrograms per litre (mg/l) and abnormal liver function test results (raised aspartate aminotransferase (AST)).

Identifying those at risk of a genetic 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 pathogenic variants (C282Y and H63D) with high carrier frequency in White northern European populations, especially in those with Celtic heritage.
  • HH has variable disease expression: presentation may be non-specific and some affected individuals may never present with serious features.
  • In the UK population, 1 in 200 are estimated to be homozygous for C282Y variants, with the clinical penetrance being approximately 1%.
  • Males are more likely to develop clinical features than females because women lose iron through menstruation.
  • Features of iron build-up in tissue can include ‘bronze diabetes’ (diabetes mellitus and skin pigmentation), arthritis, heart failure and cirrhosis of the liver.
  • Flags for an underlying genetic diagnosis include:
    • a male pattern of affected individuals in the family history; and
    • clinical features of iron overload.

What should you do next?

  • Blood tests should be undertaken, including iron, ferritin and transferrin saturation.
  • Management of iron overload is conducted by venesection. Refer the patient to gastroenterology and/or haematology.
  • Refer to the National Genomic Test Directory under testing criteria R95.
  • Any individuals with unexplained iron overload (with transferrin saturation and serum ferritin) suggestive of HH are eligible for genomic testing.
  • If a diagnosis is confirmed, offer genomic testing to:
    • first-degree relatives (parents, siblings and adult children);
    • partners, if required to determine offspring risk; and
    • children over the age of 15 or 16 years only (the age at which genomic testing is offered to children may vary geographically), as children are rarely affected in early life.

Resources

For clinicians

References:

For patients

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  • Last reviewed: 31/05/2023
  • Next review due: 31/05/2024
  • Authors: Dr Imran Rafi
  • Reviewers: Dr Asma Hamad, Dr Kate Tatton-Brown, Dr Johanna Wong

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