Hemochromatosis is a condition characterized by the excessive storage of iron in the body. The condition is also known as iron overload.
Primary hemochromatosis is a type of hemochromatosis when there is excessive absorption of iron due to a genetic defect. Secondary hemochromatosis occurs due to some other underlying disease.
This excess iron is stored in organs, mainly liver and also in the heart, pancreas, joints, etc leading to life-threatening conditions, such as liver disease, heart problems, diabetes, etc.
Treatment includes regularly removing blood until iron levels become normal. If the disease is detected and treated before organ damage occurs, the outcome is good.
Hereditary hemochromatosis is most common in people of Northern European descent in whom the prevalence is as high as 1 in 227 individuals in the general population.
The disease is less common in African-Americans, Hispanics, and Asian-Americans.
It is seen more commonly in men than in women. Also, the disease tends to be more severe in men. This is thought to be due to the monthly blood loss that occurs through menstruation in women. As a result, iron accumulation occurs slowly in women than men, and the average age of diagnosis in women is around 10 years later than in men. Women usually do not have symptoms until menopause.
Causes of Hemochromatosis
Primary or hereditary hemochromatosis
It is caused by a mutation in a gene that controls the amount of iron the body absorbs from the food. It is the most common type of hemochromatosis.
Normally, the amount of iron absorbed from food varies according to the body’s requirement. In hemochromatosis, the body cannot control the iron level which gradually increases over time and builds up in various organs ultimately causing their damage.
Hereditary hemochromatosis is an autosomal recessive genetic disorder.
Autosomal recessive means that a person must have inherited two separate genes, one from their mother and one from their father to have the condition. If a person only inherits one hemochromatosis gene they are said to be a carrier, and do not have the condition itself, but possess the ability to pass it onto their offspring.
Read more about Genetic Inheritance-Modes and Significance
The majority of the cases occur due to mutation in the human hemochromatosis protein (HFE) gene. Rest of the cases occur due to mutations in other genes and are grouped together as “non-classical hereditary hemochromatosis” or “non-HFE related hereditary hemochromatosis”.
About 10 percent of the Caucasian population is thought to be a carrier for classic hereditary hemochromatosis.
The HFE gene shows two common mutations, C282Y and H63D.
Secondary hemochromatosis
It is not inherited and occurs due to an underlying disease like:
- Severe chronic hemolysis of any cause
- Multiple frequent blood transfusions (as required in patients of beta-thalassemia major, sickle cell anemia, myelodysplastic syndromes)
- Cirrhosis (especially related to alcohol abuse)
- Long-term liver disease
- Long-term dialysis
- Overdose of iron supplements or injections (iron poisoning)
- Excess dietary iron
- Drinking beer brewed in iron containers
Juvenile hemochromatosis
It is similar to hereditary hemochromatosis in adults. However, iron accumulation starts much earlier, and symptoms appear by 15 to 30 years of age. It is caused by mutations in the hemojuvelin or hepcidin genes.
Neonatal hemochromatosis
In this type, iron accumulates rapidly in the liver of the developing fetus. It is thought to be an autoimmune disease.
Symptoms
Hemochromatosis is often a silent condition and many cases may not display any symptoms.
Symptoms usually begin between the ages of 30 and 60, although they can occur earlier. Women usually do not have symptoms until menopause.
Initial symptoms of hemochromatosis are non-specific and include:
- weakness
- fatigue
- weight loss
- joint pain
- pain in stomach
- loss of sex drive or libido
The organs most commonly affected by hemochromatosis are the liver, heart, and pancreas. Without treatment, these organs can be damaged and can lead to premature death.
Hemochromatosis may present with the following clinical syndromes:
- Liver disease
- Heart disease
- Heart failure, irregular heartbeat (arrhythmias)
- Hormonal disturbances
- Diabetes: It occurs due to the deposition of iron in islet beta cells in the pancreas leading to the non-functioning and death of these cells.
- Hypogonadism (reduced production of sex hormones) resulting in
- loss of fertility in men
- inability to get or maintain an erection (erectile dysfunction)
- irregular or absence of menstruation in women
- Arthritis
- The deposition of iron in joints may lead to joint pains. There can be pain and stiffness in the joints, particularly in the joints of the second and middle fingers
- Bronzing of the skin
- Deposits of iron in skin cells can make the skin appear bronze in color. Insulin insufficiency which occurs due to pancreatic damage also results in the deep tan color of the skin. Hence this condition is also called bronze diabetes.
Some undiagnosed patients of hemochromatosis whose main symptom is fatigue, continue taking iron tablets for a long time without medical advice. Such supplements can pose a serious health risk to people with hemochromatosis.
Diagnosis
If a person has only non-specific symptoms, a battery of tests may be carried out to rule out other diseases that share the same symptoms. A high index of suspicion is required so that testing for hemochromatosis is considered in patients presenting with vague and persistent symptoms.
Serum iron levels
Abnormally high levels are seen in hemochromatosis
Transferrin saturation
It measures the amount of iron bound to a protein (transferrin) that carries iron in the blood. Transferrin saturation values greater than 45 percent are considered high.
Total Iron Binding Capacity or TIBC
It measures the blood’s capacity to bind iron with transferrin. It may be low, but can also be normal in hemochromatosis.
Serum ferritin
Ferritin is the protein that stores iron in the body (mainly liver). Small amounts of ferritin are present in the blood serum as well. As the amount of iron stored in the body increases, so do the levels of ferritin in the serum.
Ferritin levels are also increased in inflammatory conditions like infection, cancer, alcohol abuse, etc.
Liver function tests (LFTs)
It is done to assess inflammation and damage in the liver. Of special importance are the liver enzymes ALT and AST which are increased during liver inflammation (hepatitis).
Read more about Liver Function Tests
Genetic Testing
It is done to detect HFE gene mutation in the case of suspected hereditary hemochromatosis. Genetic testing is also recommended for all first-degree relatives of a person diagnosed with hereditary hemochromatosis to see if they are a carrier or could develop the disease.
Liver Biopsy
A tiny piece of the liver is taken after passing a fine hollow needle through the skin into the liver. This small liver sample is then studied under a microscope. It is done for the following purposes
- To confirm the diagnosis of hemochromatosis in case of high serum ferritin.
- To assess the severity of liver damage or cirrhosis
- For chemical analysis of the iron concentration in the tissue sample. This is useful in secondary hemochromatosis who test negative in genetic testing.
Read more about Liver Biopsy – Types, Indications, and Procedure
Imaging techniques
Magnetic Resonance Imaging or MRI is used to provide detailed cross-sectional images of the liver as well as heart, joints, and pituitary gland. It can detect signs of organ damage.
FerriScan is an MRI-based method of measuring liver iron concentration. It provides a non-invasive and accurate method of assessing the presence and severity of iron overload.
Treatment
There is no definite cure for hemochromatosis. Treatments aim at reducing the amount of iron in the body.
Phlebotomy/venesection

Primary treatment consists of regular phlebotomies (bloodletting or removing some of the blood).
Initially, the phlebotomies may be performed every week or fortnight, until iron levels can be brought to normal range. This is called the induction phase and may take up to a year or more.
Once the iron levels are within the normal range, blood may be removed every two to three months. This is called the maintenance phase and is usually needed for the rest of the patient’s life.
During one phlebotomy session, about 450 to 500 ml of blood is removed. This amount will contain 220 mg of iron. Removal of blood activates the remaining iron stored in the body to make new red blood cells.
Read more about Phlebotomy- Indications, Procedure and Complications
Chelating agents
These are drugs that bind with iron present in the blood and promote its elimination in urine and feces. It is used in cases in whom it is difficult to remove blood regularly as in patients with anemia, cardiac disease or those with very thin or fragile veins.
Deferoxamine is the most commonly used iron-chelating drug used. Deferasirox and deferiprone are two newer chelating agents.
Dietary changes
- A diet low in iron is generally recommended. Also, they should prefer non-heme iron ( present in plant-based foods) in their diet which is less easily absorbed by the body. Food items containing heme iron such as red meat, etc should be avoided.
Read more about 50 Iron Rich Foods You Can Add To Your Diet
- Avoid taking iron and vitamin C supplements (vitamin c increases absorption of dietary iron)
- Avoid drinking excessive amounts of alcohol as it can increase the level of iron in the body.
Long Term Prognosis
In case, the disease is detected early, adequately treated, and no organ damage occurs, patients usually have a normal life expectancy.
If the serum ferritin is very high (>1000 ug/L) at diagnosis, there is a risk of liver damage and cirrhosis which may reduce the patient’s life span. Cirrhosis also increases the risk of hepatocellular carcinoma.
References
- Franchini, Massimo (2006). “Hereditary iron overload: Update on pathophysiology, diagnosis, and treatment”. American Journal of Hematology. 81 (3): 202–9. doi:10.1002/ajh.20493.
- Pietrangelo, Antonello (2010). “Hereditary Hemochromatosis: Pathogenesis, Diagnosis, and Treatment”. Gastroenterology. 139 (2): 393–408. doi:10.1053/j.gastro.2010.06.013
- Hoffbrand, A. V. (20 March 2003). “Role of deferiprone in chelation therapy for transfusional iron overload”. Blood. 102 (1): 17–24. doi:10.1182/blood-2002-06-1867.
- Kowdley, KV (November 2004). “Iron, hemochromatosis, and hepatocellular carcinoma”. Gastroenterology. 127 (5 Suppl 1): S79–86. doi:10.1016/j.gastro.2004.09.019