Primary siderosis, hemosiderosis, siderophilia, iron storage disease
Hemochromatosis is a disease in which there is an increased absorption of iron in the upper small intestine.
This increased uptake of iron means that the total iron in the body increases from 2-6g to values of up to 80g.
This iron overload has the consequence that iron deposits form in many different organs such as the heart, liver, spleen, pancreas, thyroid and the so-called pituitary gland, which impair organ function over a long period of time.
Epidemiology / frequency distribution
Hemochromatosis is a rare disease.
About 0.3-0.5% of the northern European population are affected by this disease.
Only people who are inherited (homozygous) Have a genetic defect. About 10% of the Northern European population are mixed-blooded for the HFE gene defect. It is currently estimated that around 200,000 people in Germany have hemochromatosis.
It can also happen that inherited people for the HFE gene defect do not even develop the disease. This is due to the different penetrance of the disease.
Men get sick 5-10 times more often than women, because women lose blood every month and thus also iron.
The majority of sufferers develop hemochromatosis between the 4th and 6th decades of life.
Like many diseases in internal medicine, hemochromatosis can be divided into a primary and a secondary form:
- In this sense, primary means that hemochromatosis is the underlying disease, while in secondary hemochromatosis another causal disease is responsible for the iron overload.
Primary hemochromatosis belongs to the group of hereditary diseases. In this case, incorrect information is contained in the genome, which upsets the normal iron balance.
Since it is also important to know how this hereditary disease behaves genetically, hemochromatosis is given the additional name of a autosomal recessive Hereditary disease.
This means that the disease can only manifest itself when two people who have the same genetic defect have a child.
In contrast to the recessive hereditary diseases, there are the dominant hereditary diseases.
Here it is sufficient if one parent has the incorrect information for a gene.
As mentioned above, a certain gene is defective in a hereditary disease, which can then lead to the disease becoming manifest.
In 80% of hemochromatosis patients there is a mutation in the so-called HFE gene:
The HFE gene contains the information for a protein which is referred to in technical jargon as the hereditary hemochromatosis protein.
The function of this protein is that it initiates the production of another substance, namely hepcidin. The hepcidin, together with other proteins, prevents the absorption of ice from the intestines. If the HFE protein is disturbed, no hepcidin can be produced and the intestine can absorb iron unchecked.
The body is dependent on removing iron from the intestine, as it is not given any further possibilities for iron excretion.
Secondary hemochromatosis arises from another pre-existing underlying disease:
- This acquired iron overload can, for example, simply be the result of excessive iron intake through food.
This occurs more frequently in the southern Sahara region, where spirits are distilled in iron vessels.
- In other cases, for example, blood transfusions, which are usually used in the context of anemia, can lead to secondary hemochromatosis.
- Hemolysis (destruction of the red blood cells) can also lead to iron overload, as the iron released from the red blood cells accumulates in the body.
The symptoms of hemochromatosis result from increased iron deposition in various organs, which leads to cell damage.
Among other things, there are deposits in:
- Pituitary gland
- Heart and
At the beginning of the disease, those affected usually do not notice any symptoms or changes. Symptoms only appear after several years.
- In men, the initial symptoms usually manifest themselves between the ages of 30 and 50.
- In women, on the other hand, the first symptoms appear after the menopause, as excess iron before menopause can naturally be excreted through menstruation and an increased iron requirement can be present due to pregnancy and breastfeeding.
Typical are unspecific initial symptoms such as:
- depressive mood
- Upper abdominal pain and
- Joint discomfort
The joint complaints mainly affect the index and middle fingers in the metacarpal joints. But larger joints such as the knee joint are also often affected. The joint complaints often hardly improve under therapy, which can lead to a strong reduction in quality of life.
The fact that there is, among other things, increased iron deposition in the liver, leads to an increase in the connective tissue in the liver, which is technically known as liver fibrosis.
The liver enzymes increase and the liver enlarges. If the liver is then also remodeled with scarring, it is called cirrhosis of the liver. In the further stage, the cirrhosis of the liver turns into a small cell liver carcinoma in extreme cases.
The function of the liver is restricted by the connective tissue remodeling.
In addition, there may be other typical symptoms that do not necessarily have to occur in every patient. This includes, among other things, increased skin pigmentation on sun-exposed skin areas.
In the further course, the skin turns bronze. This is due to increased melanin production (=Skin pigment) because melanin is formed from iron, among other things.
Symptoms of sugar disorder, such as increased urination and an increased feeling of thirst, can also occur. The fact that the pancreas is damaged by the iron deposition actually leads to the development of diabetes mellitus in the advanced stages (Sugar disease).
This can lead to increased hair loss and premature gray coloration of the hair.
It can also lead to impotence and in women menstrual bleeding can change or even stop completely.
Deposits in the pituitary gland often lead to a testosterone deficiency in men with a resulting reduced libido (Lust) and in women for premature menopause.
Furthermore, iron deposits in the heart muscle can lead to heart failure with resulting shortness of breath and cardiac arrhythmia.
In addition, osteoporosis can develop.
Carcinomas such as liver carcinoma or pancreatic cancer may also develop as part of the toxic cell damage caused by the iron deposits in the organs.
Read more on the topic:
- Symptoms of hemochromatosis
What are the symptoms on the skin?
Typically, patients with hemochromatosis have brownish-bronze pigmentation (discoloration) of the skin.
This darker skin color is mainly found on the areas of the skin that are exposed to sunlight:
- Extensor side of arms and hands,
- Lower leg.
In addition, the nipples, armpits, palms of the hands and the genital region are also affected by the dark pigmentation.
75% of patients with hemochromatosis have pigmentation in the armpits, and there is also no armpit hair.
All other darker skin areas are also hairless in hemochromatosis. The hyperpigmentation is due to an overproduction of the dye melanin, which often occurs in hemochromatosis.
What are the symptoms of the eyes?
Symptoms of the eyes are (so far) not known in hemochromatosis.
There are only individual case reports on hemochromatosis and cataracts (cataracts).
Hemochromatosis is not to be confused with Wilson's disease, a copper storage disease in which copper is deposited in a ring on the edge of the iris, which is called the Kayser-Fleischer corneal ring.
What are the symptoms of the joints?
In around 50% of hemochromatosis patients, the disease manifests itself as a so-called arthropathy. '
Arthropathy means nothing more than joint disease. Arthropathy in hemochromatosis is painful and occurs primarily on the metatarsophalangeal joints of the index and middle fingers.
The middle and wrist joints are also frequently affected.
An early onset of hip and knee arthrosis is also known in hemochromatosis patients.
Therapy with bloodletting can unfortunately only prevent the occurrence of joint diseases caused by hemochromatosis in the early stages; already existing joint damage cannot be reversed by the treatment.
Would you like to know how to recognize osteoarthritis? To do this, read our article:
- Symptoms of osteoarthritis
If hemochromatosis is suspected symptomatically, blood is taken for the first investigation and it is checked whether the transferrin saturation is above 60% and whether the serum ferritin is above 300ng / ml.
Transferrin serves as an iron transporter in the blood, while ferritin takes over the function of an iron store in the body.
You might also be interested in these topics: Ferritin and ferritin level too high
If both values are elevated, a genetic test is carried out, as around 0.5% of the population are homozygous carriers (on both copies of the gene) the condition for hemochromatosis.
Every eighth to tenth northern European has the system on a gene and can therefore inherit the system.
If the genetic test is positive, bloodletting therapy is usually carried out. If the genetic test is negative, an MRI image of the liver is made to detect iron deposits in the liver.
If this is positive, bloodletting therapy is also carried out.
Additional organ function tests can also be carried out.
If hemochromatosis is ultimately diagnosed, it is advisable to also carry out a genetic test on close relatives such as siblings in order to detect a disease in them as early as possible.
How does the genetic test work?
For the genetic test, blood is first drawn after the patient has given his or her specific consent.
You need a so-called EDTA blood tube with at least 2ml blood.
Any doctor can remove this blood tube and send it to a laboratory to do the genetic test.
The testing of relatives of a hemochromatosis patient is only permitted after a genetic consultation.
The blood is examined in the laboratory using PCR (polymerase chain reaction) and / or RFLP (restriction fragment length polymorphism, “genetic fingerprint”).
These test procedures look for genetic mutations in the affected HFE gene.
90% of patients have a C282Y mutation in both gene regions.
A result can be expected after about 2 weeks of processing.
What does the genetic test cost?
If the genetic test is carried out on suspicion of hemochromatosis, the health insurance company will cover the costs.
A genetic test arranged at the patient's request, although there are no symptoms, can only be carried out after consultation with a human geneticist and must be paid for by the patient himself. The costs for this vary.
It is best to ask the laboratory to which the family doctor or gastroenterologist sends the samples for the costs.
What changes are there in the blood values?
In order to better understand the blood values in hemochromatosis, here is an explanation of the important laboratory values that are changed in this disease:
This value describes the concentration of iron in the blood serum and is subject to strong fluctuations depending on the time of day, which is why ferritin allows a better statement about the iron balance of the patient.
The serum iron is needed to calculate the transferrin saturation (see below).
Ferritin is also known as "storage iron" because this protein stores iron in a biological form.
The ferritin level measurable in the blood is related to the body's iron stores.
The following applies: high iron reserves → high ferritin, low iron reserves → low ferritin.
The normal values depend on age and gender.
In hemochromatosis, the ferritin level is increased because the body's iron stores are full or even overfilled. The values in hemochromatosis are over 300 µg / l and can be increased to 6,000 µg / l.
Ferritin is also increased in various inflammatory processes in the body, so the diagnosis “hemochromatosis” cannot only be made if the ferritin value is too high.
Read more about elevated ferritin levels at: Ferritin level increased
Transferrin is a transport protein for iron. It ensures the transport of iron between the intestines, iron stores and the places of blood production where it is required for the production of hemoglobin, the red blood pigment.
The normal value for transferrin is 200-400 mg / dl.
However, the transferrin saturation is more meaningful than the transferrin level.
This value is calculated from serum iron and transferrin and describes the proportion of transferrin in the blood that is currently occupied with iron (i.e. currently transports iron from A to B within the body).
With hemochromatosis, this value is increased:
Women have values over 45%, men over 55%. The reason is the increased absorption of iron and thus the increased need to distribute this iron within the body.
Normal transferrin saturation has a high probability of preventing hemochromatosis.
The therapy of hemochromatosis consists of a reduction in body iron.
This is mostly made possible with the relatively old therapy of bloodletting.
The phlebotomy therapy consists of two phases:
- The initial therapy begins with bloodletting of 500 ml blood each time in order to lower the ferritin level to below 50 g / l.
- The long-term therapy serves to maintain the low ferritin level and includes about 4-12 bloodletting of 500 ml per year. This is to prevent iron overload in the body in hemochromatosis. Approximately 200 mg of iron are withdrawn from the body per bloodletting.
It is important that these bloodletting take place regularly in order to ensure even blood regeneration.
Dietary measures also play an important role in hemochromatosis, as foods that contain a lot of iron should be reduced.
These foods include, for example:
- Meat and
Beverages containing vitamin C increase iron absorption, especially if you eat iron-rich foods at the same time. Therefore, the vitamin C should be taken two hours after eating.
Alcohol also increases the absorption of iron in the gastrointestinal tract and should therefore also be avoided.
Drugs from the class of proton pump inhibitors (which inhibit gastric acid production) prevent iron from being reabsorbed in the intestine.
If other organs are already affected, they must of course also be treated therapeutically.
In special cases of hemochromatosis, in which, for example, the heart function is severely impaired, iron binders must be used because the heart is unable to handle the reduced blood volume (caused by bloodletting) to compensate with an increased heartbeat.
In those cases in which the liver is severely damaged (cirrhosis of the liver), an organ transplant must be considered.
The bloodletting therapy
Hemochromatosis is treated with bloodletting therapy. This can be very stressful for the patient. The overfilled iron stores are emptied by bloodletting.
At the beginning of the treatment, about 500ml of blood is drained every one to two weeks.
The bloodletting therapy is continued until the serum ferritin reaches a value below 50 µg / l.
In advanced hemochromatosis, this can take one to two years.
This is followed by the so-called maintenance phase, in which bloodletting is only required every three months in order to keep the ferritin at a value between 50 and 100 µg / l.
Since hemochromatosis is mostly genetic and the cause cannot be eliminated, the therapy must be continued for a lifetime.
In addition to bloodletting therapy, drug therapy is also possible, but bloodletting therapy is more effective and has fewer side effects.
How do I eat properly if I have hemochromatosis?
It is important to avoid an accumulation of iron through diet so as not to negate the effect of the bloodletting therapy.
You should therefore avoid foods with a high iron content such as animal innards.
Otherwise there are actually no restrictions in terms of nutrition.
Drinking black tea or milk with meals to a small extent decreases the absorption of iron in the small intestine and can therefore be helpful for people with hemochromatosis.
Since vitamin C favors the absorption of iron from food, fruit juices containing vitamin C should not be drunk about 2 hours before and after meals.
It is important to avoid alcohol after the diagnosis has been made until the iron stores are depleted (after approx. 1 to 1.5 years of bloodletting therapy).
In addition, it makes sense to avoid alcohol in order to limit the damage to the liver cells.
Can I drink alcohol if I have hemochromatosis?
The iron overload caused by hemochromatosis damages the liver and in three quarters of patients leads to cirrhosis of the liver, irreversible damage to the liver with scarring and loss of function.
If you drink alcohol regularly, this also damages the liver cells and can also cause cirrhosis of the liver.
Hemochromatosis patients should avoid alcohol for several reasons:
Regular alcohol consumption can interfere with the iron metabolism and (even if there is no hemochromatosis) also lead to iron overload.
The effects then add up.
Regular alcohol consumption causes an additional iron overload in hemochromatosis patients. To prevent additional damage to the liver in hemochromatosis, patients with this disease should refrain from regular alcohol consumption.
After the diagnosis until the iron stores are emptied through regular bloodletting, alcohol should be completely avoided.
What are the side effects of regular bloodletting?
Typical side effects of bloodletting therapy are
- Fatigue and
The cause is the volume that the body then lacks.
If these symptoms occur frequently after bloodletting, an infusion can be given to make up for the fluid that has been lost.
Alternatively, the bloodletting can be divided into several sessions in which less blood has to be drawn.
The prognosis of hemochromatosis depends most on the accompanying damage to the affected organs.
In most cases the liver is damaged by the increased iron storage. This often leads to the picture of cirrhosis of the liver.
Cirrhosis of the liver develops especially when the hemochromatosis remains undetected for a long time.
The main complication of cirrhosis in the development of liver cancer, which in itself has an unfavorable prognosis. The longer the iron overload persists, the higher the likelihood that the organs, especially the liver, will be damaged.
About 35% of patients with significant haemochromatosis develop liver cell cancer later on.
How does hemochromatosis affect life expectancy?
If the hemochromatosis is discovered in the latent stage, in which liver cirrhosis does not yet exist, and appropriately treated with bloodletting therapy (therapy goal is serum ferritin <50 µg / l), the life expectancy of the affected patient is not restricted.
Proper therapy can prevent iron from building up in the liver and damaging liver cells.
However, if the disease is only diagnosed after irreversible damage to the liver has occurred, life expectancy is significantly reduced; depending on the severity of the liver cirrhosis, the one-year survival rate is between 35-100 percent.
Hemochromatosis and cirrhosis of the liver
The liver is severely affected in hemochromatosis.
90% of patients develop an enlarged liver (hepatomegaly) as a result of the disease.
In many patients (up to 75% of cases), liver cirrhosis develops over time.
Liver cirrhosis is an irreversible disease of the liver tissue with scarred remodeling and impaired function. Once it has occurred in hemochromatosis patients, it can only be eliminated with a liver transplant.
Liver cirrhosis increases the risk of liver cancer significantly.
Would you like to find out more about cirrhosis of the liver? To do this, read the article on:
- Therapy of cirrhosis of the liver
Hemochromatosis and diabetes mellitus
Iron storage in hemochromatosis affects not only the liver but many other organs as well. Among other things, the pancreas, which produces the hormone insulin, is affected.
Insulin is essential for the sugar metabolism.
The pancreas is damaged by the storage of iron, which means that the production of insulin decreases or can stop entirely.
If this is the case, one speaks of so-called “bronze diabetes”, a form of diabetes mellitus (“diabetes”) in which insulin has to be replaced in order to maintain the sugar metabolism.
Diabetes mellitus occurs in up to 70% of cases in hemochromatosis patients.
You are not sure whether you may also be affected by this accompanying disease? Read our article on this:
- How do I recognize diabetes?
Hemochromatosis and polyneuropathy
Polyneuropathy describes damage to the nerves in which several nerves (usually the legs and / or arms) are affected.
It is not one of the typical and well-studied side effects of hemochromatosis.
There are only a few studies on this subject with small numbers of patients.
There are studies that suggest a connection between hemochromatosis and polyneuropathy, but also studies that describe a protective effect of hemochromatosis on the development of polyneuropathy during therapy with HIV drugs.
What is certain, however, is that with advanced hemochromatosis and diabetes mellitus, a diabetic polyneuropathy can occur as a secondary disease.
Read more about this at:
- Diabetic neuropathy
Hemochromatosis and dark circles
The skin under the eyes is very well supplied with blood, as many small blood vessels are involved in the supply. In addition, this region of the body has hardly any subcutaneous fatty tissue and is so thin that these blood vessels can easily shine through.
If there is an iron deficiency, the resulting anemia can reduce the oxygen content in the blood, making the blood appear darker and then appear as a ring under the eyes through the thin skin under the eye.
Dark circles are not a typical symptom of hemochromatosis, but can occur together with other symptoms (e.g. fatigue) in the case of iron deficiency due to too much bloodletting.
The first indications regarding the appearance of hemochromatosis were given by a Mr. Armand Trousseau in the 19th century.
He described a complex of symptoms consisting of cirrhosis of the liver, diabetes and dark skin pigmentation.
20 years later the term hemochromatosis was coined.
In the 1970s, the autosomal recessive mode of inheritance was recognized, and the causative gene (HFE gene) was finally discovered in the 90s.
Scientists believe that the mutation of this gene offered a survival advantage in times of malnutrition, as the iron was stored more.
Hemochromatosis is a metabolic disease in which there is an increased storage of iron in the organs and tissues of the body.
Hemochromatosis belongs to the large group of hereditary diseases and is based on a genetic defect in the so-called HFE gene, which is responsible for regulating the absorption of iron from the intestine.
These iron deposits damage organs and tissues and can build up in the skin and cause a bronze-colored discoloration. The organs that are affected are mainly the heart and the liver.
If hemochromatosis remains undetected, cirrhosis of the liver can develop and ultimately liver cell carcinoma.
Therapeutic measures include bloodletting and dietary iron restriction.
Bloodletting lowers the diagnostically important ferritin value in order to reduce the amount of body iron. The prognosis of hemochromatosis depends on the accompanying diseases and essentially on the extent of the liver damage.
About 35% of hemochromatosis patients develop liver carcinoma due to liver cirrhosis.
Recommendations from the editorial team
- Symptoms of hemochromatosis
- Cirrhosis of the liver - you should know that
- Everything about diabetic neuropathy
- Ferritin level too high
- Genetic test