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Hereditary Hemochromatosis - Causes, Symptoms, Diagnosis, and Management

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Hereditary hemochromatosis is a genetic defect that leads to the deposition of iron in organs, causing dysfunction. The condition is explained in the article

Medically reviewed by

Dr. Kaushal Bhavsar

Published At October 5, 2022
Reviewed AtMarch 2, 2023


Hemochromatosis is a disease associated with the deposition of excess iron in the body, which can cause multiple organ dysfunctions. In normal conditions, the body strictly regulates iron absorption due to the incapability of excreting excess iron. Hemochromatosis occurs when there is a high alcoholic concentration of iron deposition in the body. The condition is also known as ‘bronze diabetes’ due to the discoloration of the skin. Hereditary hemochromatosis is a very common disorder affecting whites, whereas secondary hemochromatosis occurs due to erythropoiesis disorders. The treatment for secondary hemochromatosis is blood transfusions. Secondary hemochromatosis is mainly caused due to thalassemia, hereditary spherocytosis, sickle cell anemia, pyruvate kinase deficiency, and sideroblastic anemia.

What Are the Causes of Hereditary Hemochromatosis?

The main cause of hereditary hemochromatosis is a mutation of the hemochromatosis gene (HFE) protein. A mutation in the HFE gene leads to increased iron absorption despite a normal dietary intake. H63D and C28Y are the most common mutations of the HFE gene.

The different types of hereditary hemochromatosis are:

  • Type 1 (HFE Related): It is the classic form of hereditary hemochromatosis, which is inherited in an autosomal recessive pattern.

  • Type 2a (Mutations of Hemojuvenile Gene) and Type 2b (Mutation of Hepcidin Gene): It is an autosomal recessive disorder that is seen in both whites and non-whites. The onset of this type is at the age of 15 to 20 years.

  • Type 3 (Mutations of Transferrin Receptor-2 Gene): It is an autosomal recessive disorder that is seen in both whites and non-whites, and the onset of the disease is 30 to 40 years.

  • Type 4 (Mutation of the Ferroportin Gene): Autosomal dominant disease is common in both whites and non-whites, and the onset is 10 to 80 years old.

The retained iron is primarily deposited in the parenchymal cells in cases of hereditary hemochromatosis, whereas in cases of transfusional hemochromatosis, it is deposited in the reticuloendothelial cells. This excess iron is deposited in the cells as hemosiderin which eventually leads to cell death and replacement of the cells by a fibrous deposition which leads to impairment or destruction of organs.

What Is the Epidemiology of Hereditary Hemochromatosis?

Hereditary hemochromatosis is the most common autosomal recessive disorder in whites, with the prevalence of one case in every 300 to 500 individuals. The white population has a six times higher chance of developing the disease than blacks. Men are affected more than women in cases of hemochromatosis.

What Are the Signs and Symptoms of Hereditary Hemochromatosis?

The signs and symptoms of hereditary hemochromatosis depend on the organ system affected. Patients are generally asymptomatic until adulthood, and diagnosis is made only when multiple systems are affected. Women with hemochromatosis show symptoms in later life than men due to blood loss and consequent iron excretion along with menstruation. The early manifestations of the disease include fatigue, arthralgias, or lethargy. The late manifestations are seen when iron starts accumulating in the tissues gradually.

The late symptoms are:

  • Secondary Diabetes: The lateral aspects of the nails reveal finger prick marks which indicates diabetes, and abdominal examination suggests lipodystrophy.

  • Koilonychia: Soft nails which look scooped out and are known as spoon nails. Koilonychia affects the thumb and index fingers in 50% of patients and affects all the nails in approximately 25% of patients.

  • Discoloration of the Skin: It is known as diffused hyperpigmentation, which is seen in almost 90% of patients. It is one of the earliest manifestations of the disease. The condition is generally mild; however, it gets more evident in sun-exposed areas of the skin. Other skin manifestations include ichthyosiform changes and skin atrophy on the anterior aspects of lower limbs.

  • Liver Involvement: Liver disease can present with abdominal pain, cirrhosis, hepatomegaly, ascites, portal hypertension, and splenomegaly. The risk of hepatocellular carcinoma (HCC) increases in patients with already present hemochromatosis and cirrhosis.

  • Arthropathy: Calcium pyrophosphate crystal deposition in the joints (pseudogout). It causes arthritis, joint swelling, and chondrocalcinosis.

  • Cardiac Involvement: Hemochromatosis can cause arrhythmias, dilated cardiomyopathy, and cardiac failure.

  • Endocrine Dysfunction: Hemochromatosis can lead to hypopituitarism, thyroid dysfunction, adrenal dysfunction, osteoporosis, and parathyroid defects. Decreased body hair or granuloma is seen in chronic liver disease and hypogonadism.

  • Cancers: Compared to the general population, the risk of cancer is 20 times higher in patients with hemochromatosis.

  • Infections: Excessive accumulation of iron increases the risk of infection from Yersinia enterocolitica, Vibrio vulnificus, and monocytogenes.

How to Diagnose Hereditary Hemochromatosis?

  • The evaluation starts with the measurement of serum ferritin concentration and serum transferrin saturation. Ferritin levels above 200 mcg/L in women and 300 mcg/L in men or transferrin saturation of more than 40% in women and 50% in men indicates further testing.

  • Radiographs are used to diagnose organs involved, such as echocardiography to look for cardiomyopathy. A chest radiograph indicates cardiomegaly and increased pulmonary vascular markings.

  • First-degree patients with hereditary hemochromatosis should undergo screening with genetic testing.

How to Treat Hereditary Hemochromatosis?

  • The treatment of choice for primary hemochromatosis is phlebotomy. The red blood cells are drawn off, which minimizes iron toxicity. Patients may require 50 to 100 phlebotomies of 500 ml each to get normal iron levels in the body. Initially, phlebotomy is performed once or twice a week when the iron levels come down to normal; it is required three too four times a year for a lifetime. The objective behind this treatment is to reach a ferritin level of less than 50 mcg/L. Iron removal through phlebotomy improves insulin sensitivity, fatigue, and skin pigmentation. It does not show any effect on hypogonadism, cirrhosis, and arthropathy.

  • Organ damage is not reversed by phlebotomy. Organ dysfunction requires associated treatments such as insulin for pancreatic dysfunction.

  • Chelation is not seen to be very effective in hereditary hemochromatosis; it is more beneficial in erythropoietic hemochromatosis, where phlebotomy is not an option.

  • Erythropoietin is sometimes administered in combination with phlebotomy to maintain hemoglobin concentration while forcing iron mobilization.

Which Diseases Are Similar to Hereditary Hemochromatosis?

  • Chronic Transfusion: Iron overload due to chronic transfusion.

  • Dysmetabolic Hyperferritinemia: Insulin resistance associated with iron overload.

  • Alcoholic Liver Disease: Over-consumption of alcohol leads to liver damage and symptoms such as scarring, inflammation, and fat accumulation.

  • Hereditary Aceruloplasminemia: Accumulation of iron in the brain and other organs.


Hereditary hemochromatosis is a genetic disorder that leads to iron accumulation in organs such as the liver. It causes many conditions such as skin discoloration, liver cirrhosis, or diabetes. The treatment of choice for the disorder is phlebotomy. Treatment for organ dysfunctions depends on the organ involved and the severity of the damage.

Frequently Asked Questions


Describe Hereditary Hemochromatosis?

Hereditary hemochromatosis is a condition that makes the body absorb too much iron from the food that a person consumes. The excessive amount of iron is then stored in the organs, especially in the liver, heart, and pancreas. Therefore, too much iron can lead to life-threatening conditions, which include heart problems, diabetes, and liver conditions.


What Are the Types of Hemochromatosis?

There are four types of hemochromatosis, which include -
Type 1 - It is the most common form of hereditary hemochromatosis, which is inherited in an autosomal recessive pattern.
Type 2 - This type appears in childhood, and it affects the sex hormones as the person grows. Girls may have regular periods, but the periods may stop after a few years. In the case of boys, puberty may be delayed.
Type 3 - The onset is seen in 30 to 40 years and may be a mix of type 1 and 2.
Type 4 - Symptoms may appear in adulthood, and the symptoms may appear between the ages of 40 and 60.


What Is the Primary Cause of Hemochromatosis?

Hemochromatosis is commonly caused by a mutation in a certain gene. The gene affected in this condition is the hemochromatosis gene (HFE) protein, which affects the body's ability to absorb iron from food. If a person inherits the two of defected gene variants from each parent,, there is a high chance that he or she may develop hereditary hemochromatosis and be at risk for developing high iron levels.


What Organs Are Affected by Hereditary Hemochromatosis?

Hereditary hemochromatosis is a multiple-organ system dysfunction. In this disorder, there is excess iron deposition in the body, thus affecting various organs in the body, such as the liver, pancreas, heart, thyroid, joints, skin, gonads, and pituitary.


What Is the Ideal Treatment for Hereditary Hemochromatosis?

The most common treatment of hereditary hemochromatosis is regularly removing the blood from the body. This process is called phlebotomy. This is the same as donating blood, which will help lower iron levels in the body. The amount and frequency of blood removal depend on age, overall health, and the severity of iron overload.


What Are the Clinical Features of Hereditary Hemochromatosis?

The clinical features of hereditary hemochromatosis include -
- Joint pain.
- Abdominal pain.
- Fatigue.
- Weakness.
- Liver cirrhosis.
- Diabetes.
- Heart failure.
- Loss of libido (sex drive).
- Impotence.
- Liver failure.
- Bronze or gray skin color.
- Memory loss.


What Iron Levels Indicate Hemochromatosis?

The iron levels of more than 300 ng/mL (nanograms per milliliter) in males and above 200 ng/mL in females indicated hemochromatosis. However, the body's high ferritin (iron) levels may also occur due to some other conditions. Therefore, further testing has to be done to confirm the diagnosis.


Is Hemochromatosis a Serious Disease?

Hereditary hemochromatosis is a genetic condition that may cause severe complications, like severe liver and heart problems. Early diagnosis and treatment are essential to prevent such complications, as high levels of iron can damage multiple organs of the body, and the damage may be irreversible, including scarring of the liver (cirrhosis) or liver cancer.


What Is the Most Common Age for Hemochromatosis?

The most common type of hemochromatosis is type 1 or type 4. These are usually present at birth, but the symptoms do not appear until later. Usually, the symptoms may be noticed after 40 years in men and 60 years in women. The symptoms usually appear in women after menopause, when the iron is not removed from the body with menstruation and pregnancy.


Can Hemochromatosis Cause High Hemoglobin?

According to various studies, it has been found that elevated hemoglobin is considered a feature of hereditary hemochromatosis. The mean hemoglobin value in patients with hemochromatosis is 15.0 mg/dL (milligrams per deciliter). Usually, a high hemoglobin count indicates an above-normal level of iron-containing protein in red blood cells.


How to Naturally Flush Iron Out of the Body?

The human body cannot get rid of excess iron. That's why iron is different from other minerals present in the body. However, some iron is lost during some processes, like the shedding of skin cells. In the case of the buildup of excess iron or any other mineral in the body, the body will simply excrete it to prevent overload.


Can a Person Live a Normal Life With Hemochromatosis?

The majority of patients affected by hemochromatosis usually have a normal life expectancy. However, they do need to keep a regular check on their iron levels. Moreover, the life span may be affected in people who do not get treatment for hemochromatosis and may develop liver cirrhosis or diabetes mellitus later in life.


What Are the Risk Factors for Hemochromatosis?

Certain factors that may increase the risk of hemochromatosis include -
- People belonging to Northern Europe are more prone to hereditary hemochromatosis than people of other ethnic backgrounds. Moreover, hemochromatosis is less common in people of black, Hispanic, and Asian ancestry.
- Men are more prone to hemochromatosis than women.
- Family history with hemochromatosis also plays a major role in causing hemochromatosis.


What Type of Cancer Causes High Iron Levels?

High levels of iron may occur due to certain cancers, which include -
- Neuroblastoma (cancer found in adrenal glands found on top of kidneys).
- Hodgkinson's lymphoma (cancer affecting the lymphatic system).
- Cervical cancer (cancer of the cervix, the lowermost part of the uterus). 
- Oral squamous cell carcinoma (cancer of the oral cavity), 
- Renal cell cancer.
- T cell lymphoma (a rare type of cancer of T cells, a type of white blood cells). 
- Breast cancer.
Dr. Kaushal Bhavsar
Dr. Kaushal Bhavsar

Pulmonology (Asthma Doctors)


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