Healthy people absorb the exact amount of iron that they lose through sweat, stool and urine. People suffering from hemochromatosis absorb more than the required amount of 1 to 2 milligrams per day.
This overcompensation results in an increased iron content in the body - up to 3.5 grams in men and 2.2 grams in women. The excess iron is mainly stored in
is deposited. Organ damage occurs from a body iron content of more than five times the normal value.
In men, the first symptoms usually occur between the ages of 30 and 50, in women a little later.
In the early stages, there are hardly any symptoms of haemochromatosis. This is why the diagnosis is often made late.
Thefirst signs are
- Tiredness and a feeling of weakness,
- vague pain in the upper abdomen,
- pain in the metacarpophalangeal joints of the middle and index fingers,
- dark skin pigmentation, especially in the axillae, and lack of hair in this area, later bronze tint,
- Signs of diabetes mellitus, e.g. increased thirst and urination as well as weight loss,
- impotence, altered and/or absent menstruation.
The increasing deposition of iron in the liver initially leads to a remodeling of the specific liver tissue into connective tissue(fibrosis). Without treatment, additional scarring remodeling(liver cirrhosis) occurs in the further course.
The staging of hemochromatosis is also based on these remodeling processes:
- latent, pre-cirrhotic stage (before the development of cirrhosis)
- manifest, cirrhotic stage (cirrhosis has developed)
If left untreated, haemochromatosis leads to liver fibrosis and ultimately to cirrhosis © nmfotograf | AdobeStock
In haemochromatosis, iron overload is usually the result of dysregulation. This in turn is caused by various genetic defects.
A distinction is made, depending on
- the underlying genetic defect and its inheritance,
- the onset of the disease and
- the symptoms present,
four types of haemochromatosis. Type I is the most common form.
In types 1 to 3, the underlying gene mutation is passed on in an autosomal recessive manner. Autosomal recessive means that the disease only manifests itself if the mutation is inherited from both parents. If it is passed on by only one parent, the affected person does not develop the disease. However, he or she becomes a carrier who can pass on the disease.
Haemochromatosis type 4 is inherited autosomal-dominantly. This means that this type manifests itself even if the genetic defect was only inherited from one parent.
Haemochromatosis type 1
Haemochromatosis type 1 is caused by a mutation in the HFE gene. The exact mechanisms that lead to iron overload as a result of this genetic defect have not yet been clarified.
It is assumed that the defective HFE gene leads to a reduced concentration of the iron hormone hepcidin in the blood. The iron hormone regulates iron absorption in the intestine. If it is present in reduced concentrations, this leads to increased iron absorption and deposition.
The symptoms of type 1 can be very variable. It is therefore assumed that there are other, as yet unexplained genetic factors that lead to increased iron absorption.
However, even in the case of only moderate iron accumulation with no symptoms, additional liver toxins or diseases such as alcohol or hepatitis C can lead to severe liver damage due to the toxic effect of iron.
- Frequency: 1 : 10,000
- Age of manifestation: in men between the ages of 30 and 50, in women after the menopause due to the regulating effect of menstrual bleeding
- Organ manifestations (according to frequency): Liver (cirrhosis), pancreas (diabetes mellitus), heart (insufficiency), joints (arthralgia or pain), pituitary gland (hypogonadism or testicular dysfunction with testosterone deficiency)
Haemochromatosis type 2
Haemochromatosis type 2 is divided into subtypes 2a and 2b. While the HJV gene (haemojuvelin gene) is mutated in type 2a, type 2b is caused by an altered HAMP gene (hepcidin gene).
Like hepcidin, hemojuvelin is a regulator of iron metabolism. Both genetic defects lead to increased iron absorption in the small intestine.
- Frequency: approx. 1 : 1,000,000 (type 2a); rare (type 2b)
- Age of manifestation: 10 to 20 years of age (type 2a); 5 to 15 years of age (type 2b)
- Organ manifestations (by frequency): Heart (insufficiency), pituitary gland (hypogonadism), liver (cirrhosis)
Haemochromatosis type 3
Haemochromatosis type 3 is caused by a mutated TFR2 gene (transferrin receptor 2 gene). The transferrin receptor-2 absorbs the iron bound to the glycoprotein transferrin in the liver. The defect leads to iron deposition with tissue damage.
- Frequency: Rarity
- Age of manifestation: 10 to 50 years of age
- Organ manifestations: like type 1
Haemochromatosis type 4
This type of haemochromatosis is caused by a mutation in the SLC11A3 gene (ferroportin gene), which is why it is also known as ferroportin disease. After iron has been taken up by transport proteins into the epithelial cells of the intestine, it is absorbed there by the export protein ferroportin and transferred into the blood circulation. If the export protein is defective, the iron content in the body increases.
- Frequency: 1 : 1,000,000
- Age of manifestation: 10 to 50 years of age
- Organ manifestations (by frequency): Liver (cirrhosis), bone marrow(anemia), spleen (iron deposition)
The aim of hemochromatosis treatment is to reduce the ferritin concentration in the serum to below 50 µg per liter. In this way, doctors aim to empty the body's iron stores and prevent tissue damage. Various strategies are used for this purpose.
Bloodletting therapy
Depending on the patient's tolerance and clinical picture, a specific amount of blood is withdrawn from the patient at a certain frequency.
Typically, phlebotomies are performed once or twice a week at the start of treatment, with 400 to 500 milliliters of blood being taken each time. With 500 milliliters of blood, 250 milligrams of iron are removed from the body.
After the onset of mycrocytic anemia, the intervals between blood draws are increased. Maintenance therapy with the longest possible intervals between phlebotomies is carried out for the rest of the patient's life.
Bloodletting therapy is not possible in cases of severe anemia and heart failure.
Iron chelators
If phlebotomy therapy is not possible, or in the case of haemochromatosis before the age of 30, iron chelators such as deferoxamine and deferasirox are used to reduce the iron content in the body.
These bind the iron in the body and excrete it.
Dietary measures
A low-iron diet is not necessary in haemochromatosis. However, it is recommended to drink black tea with meals to reduce iron absorption.
Haemochromatosis is treated by specialists in internal medicine with a focus on
specialists in hematology. Phlebotomies are carried out in iron metabolism outpatient clinics.