PassFinals
Endocrinology & Metabolic

Hereditary haemochromatosis

Hereditary haemochromatosis is inherited dysregulation of iron absorption, usually from HFE C282Y homozygosity, causing progressive parenchymal iron overload; early recognition and specialist venesection can prevent irreversible liver, endocrine, cardiac and joint damage.

In a nutshell

Hereditary haemochromatosis is usually HFE-related iron overload caused by inappropriately low hepcidin. Raised transferrin saturation and ferritin prompt HFE testing and organ assessment. Venesection removes iron and can prevent progression before cirrhosis; genotype alone does not prove clinical disease.

Classic presentation

A middle-aged person with fatigue, abnormal liver tests, diabetes, reduced libido or second/third MCP arthropathy has persistent high ferritin and transferrin saturation, with HFE testing showing C282Y homozygosity.

Key points

  • Interpret ferritin with transferrin saturation because ferritin rises with inflammation and liver disease.
  • C282Y homozygosity is common in clinical HFE haemochromatosis, but penetrance is incomplete.
  • Stage liver fibrosis and assess for diabetes, endocrine, cardiac, joint and bone complications.
  • Therapeutic venesection is first-line for suitable patients; use specialist-individualised ferritin targets and maintenance.
  • Cirrhosis/advanced fibrosis carries ongoing hepatocellular-carcinoma risk, and adult first-degree relatives need cascade assessment.

First-line investigation

Transferrin saturation and ferritin with full blood count, liver tests and relevant secondary-cause assessment, followed by specialist HFE testing when biochemical overload is present.

Management

Escalate organ emergencies

  • Urgently assess decompensated liver disease, acute heart failure, arrhythmia or suspected hepatocellular carcinoma rather than treating the ferritin in isolation.3,4

Confirm iron overload

  • Measure transferrin saturation and ferritin, interpret alternative causes, and arrange HFE/genomic assessment through a specialist pathway.2,3

Remove excess iron

  • Use specialist therapeutic venesection with haemoglobin and ferritin monitoring, individualised induction and maintenance targets, and chelation only when venesection is unsuitable.4,5,6

Manage organ injury

  • Assess and treat hepatic, cardiac, endocrine, metabolic, joint and bone complications through the appropriate specialties.3,2

Protect the cirrhotic liver

  • Refer advanced fibrosis/cirrhosis to hepatology and continue hepatocellular-carcinoma surveillance according to the specialist liver pathway.4,3

Screen family and maintain depletion

  • Continue maintenance monitoring/venesection as needed, review lifestyle and supplements, and offer adult first-degree relatives cascade testing.4,2,5

Exam traps

  • A raised ferritin alone is not diagnostic; it is an acute-phase protein.
  • A positive HFE genotype without iron overload does not automatically require venesection.
  • Venesection may prevent further loading but cannot be assumed to reverse established cirrhosis, diabetes or arthropathy.
  • Do not blend older strict transferrin-saturation targets with the newer BSG/BASL ferritin-based individualised pathway.
  • Do not recommend extreme iron restriction; avoid iron/vitamin-C supplements and excess alcohol.

Illustrations

Hepatic iron on Perls Prussian blue stainA liver histology section stained with Perls Prussian blue, showing heavy blue granular iron deposition within hepatocytes.Joseph Mathew, May Y Leong, Nick Morley and Alastair D Burt, Wikimedia Commons · CC-BY-2.0

Key sources

  1. BSG-endorsed BSH guideline: diagnosis and therapy of genetic haemochromatosis (UK specialty guideline reviewed and updated in 2017, hosted by the British Society of Gastroenterology; retained as older specialist context and explicitly distinguished from newer BSG/BASL venesection best practice; accessed 4 August 2026.)Updated 1 Jan 2017
  2. NHS England Genomics Education Programme: hereditary haemochromatosis (Current UK genomic education resource covering HFE variants, incomplete penetrance, diagnostic ferritin/transferrin-saturation patterns, cascade testing and venesection; last reviewed 2 March 2026 and accessed 4 August 2026.)Updated 2 Mar 2026
  3. NHS: haemochromatosis diagnosis (NHS information on symptoms, ferritin/transferrin-saturation testing, genetic testing, organ assessment and secondary causes; last reviewed 29 March 2023 and accessed 4 August 2026.)Updated 29 Mar 2023
  4. BSG/BASL Special Interest Group: venesection treatment in haemochromatosis - current best practice (Current UK multidisciplinary best-practice description covering indications, individualised induction/maintenance venesection, monitoring, targets, adverse effects and alternatives; published 25 June 2025 and accessed 4 August 2026.)Updated 25 Jun 2025
  5. NHS: haemochromatosis treatment (NHS information on venesection, maintenance, chelation, diet, alcohol, supplements and raw-shellfish risk; last reviewed 29 March 2023 and accessed 4 August 2026.)Updated 29 Mar 2023
  6. British National Formulary (BNF) (Current UK prescribing information for iron chelators and medicines used to treat iron-related organ complications; product-specific details must be checked at the point of care; accessed 4 August 2026.)

This page is exam revision material, not medical advice, and must not be used for patient care. Always check drug doses against the BNF and current guidance. Full disclaimer.