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Causes, diagnosis and treatment

Haemochromatosis, also known as "iron storage disease", is a genetic disorder that leads to an excessive accumulation of iron in the body. In the long term, this can lead to serious damage to organs such as the liver, heart and pancreas. This page provides an overview of the causes, symptoms, diagnosis and treatment options based on current guidelines and consensus recommendations.

Causes of haemochromatosis

In most cases, hemochromatosis is caused by mutations in the HFE gene, particularly the p.C282Y and p.H63D variants. These genetic changes lead to increased iron absorption from food. There are also rarer genetic variants and acquired forms that can lead to iron overload.

Symptoms of haemochromatosis

Haemochromatosis often only becomes apparent after years, as the iron accumulation is gradual.

Common symptoms

Early stage: tiredness, joint pain (especially in the hands), abdominal pain

Late stage: liver disease (e.g. cirrhosis, liver cancer), heart problems (arrhythmias, heart failure), hormonal disorders (e.g. diabetes, hypogonadism), skin changes (darker pigmentation)

Diagnostics

Step 1: Laboratory tests

  • Transferrin saturation: Elevations above 45% in women and 50% in men indicate iron overload.
  • Serum ferritin: Values >200 µg/L in women and >300 µg/L in men are suspicious.

Step 2: Genetic tests

  • HFE mutation tests: If there is a persistent increase in iron parameters or a positive family history, a test for p.C282Y and possibly p.H63D is recommended. Informed consent is required
  • Special cases: Rare genetic variants should be tested in young patients with severe manifestations such as liver disease, cardiomyopathy or amenorrhea

Step 3: Imaging

  • MRI: Important for quantifying the iron concentration in the liver, heart and other organs. Especially in cases of unclear hyperferritinemia or suspected advanced liver disease
  • Liver stiffness measurement (elastography): Can be used to rule out advanced fibrosis

Step 4: Liver biopsy

  • Areas of application: If the cause of hyperferritinemia (>1,000 µg/L) or elevated liver values is unclear, a biopsy can be performed to assess fibrosis
  • Not recommended: For the diagnosis of iron overload or in cases of already clearly diagnosed cirrhosis

Treatment

Iron deprivation

  • Bloodletting therapy: First choice for iron overload. The goal is a serum ferritin concentration of 50 µg/L
  • Alternatives: Erythrocytapheresis can be used in special cases (consensus: 94 %). Iron chelation (e.g. Deferasirox) is a second-line therapy and only indicated in exceptional cases.

Lifestyle modifications

  • Low-iron diet: Avoidance of iron-rich and iron-fortified foods, restriction of red meat and vitamin C supplements.
  • Avoiding alcohol: especially in the case of liver disease or during the iron deprivation phase
  • Infection prophylaxis: Avoid raw seafood and contact with seawater in affected regions due to the risk of rare infections caused by siderophilic pathogens such as Vibrio vulnificus.

Long-term management

Monitoring liver health

  • Patients with cirrhosis should be screened regularly for hepatocellular carcinoma (HCC), regardless of iron depletion (every 6 months).
  • HCC screening is also recommended for advanced fibrosis (METAVIR F3)

Cardiovascular involvement

  • In case of severe iron overload or symptoms such as heart failure, a cardiologic examination (e.g. cardio-MRI) is recommended (consensus: 100%).

Pregnancy

  • Therapeutic phlebotomy can be paused during pregnancy if there is no severe iron overload (individual assessment, consensus: 93%).