Synopsis
Confirm clinically meaningful hereditary iron overload, distinguish reactive hyperferritinaemia and use safe venesection, organ assessment and family testing.
- Classic HFE haemochromatosis is an autosomal recessive disorder of inappropriately increased intestinal iron absorption, most strongly associated with C282Y homozygosity.
- Penetrance is incomplete: a genotype confers risk, while biochemical and clinical iron overload determine organ threat and treatment need.
- Transferrin saturation rises early and is central to recognising iron loading; ferritin estimates stores but also rises with inflammation, alcohol, metabolic liver disease and malignancy.
Key red flags
Hepatomegaly, raised aminotransferases, fibrosis or cirrhosis occurs with an iron-loading phenotype, often amplified by alcohol or metabolic steatosis.
Investigation priorities
Identify persistent excess circulating iron availability.
Management branches
Ferritin is elevated on routine or symptom-led blood testing.
- Review infection, inflammation, alcohol, metabolic risk, transfusions, supplements, malignancy and kidney or liver disease and obtain CRP, full blood count and liver tests.
- Measure transferrin saturation and repeat indices when clinically stable if results are borderline or discordant.
Key medicines
Therapeutic venesectionA typical induction removes approximately 500 mL of blood weekly or fortnightly, but use a smaller volume or longer interval for low body mass, older age or comorbidity and follow the current BSH and local ferritin and haemoglobin targets.
Iron chelationA specialist may select deferasirox, desferrioxamine or another chelator at its current BNF and commissioning regimen only when significant overload cannot be managed by venesection; this is uncommon and may be off-label for HFE disease.