Hereditary Haemochromatosis (HFE): Causes, Symptoms, Diagnosis & Treatment

Hereditary Haemochromatosis (HFE): Causes, Symptoms, Diagnosis, and Treatment

Complete article to Iron Overload Disorder | Symptoms, Genetics, Testing, and Management

Hereditary Haemochromatosis (HFE) is one of the most common genetic disorders affecting iron metabolism in the human body. Despite its prevalence, it remains widely underdiagnosed due to its slow progression and non-specific early symptoms. This condition leads to excessive absorption and accumulation of iron in vital organs such as the liver, heart, pancreas, joints, and skin. Over time, this excess iron can cause serious and potentially life-threatening complications.

In this comprehensive article, we will explore what Hereditary Haemochromatosis is, how it develops, its genetic basis, symptoms, diagnostic methods, treatment options, lifestyle modifications, and long-term outlook. This article is designed to be informative, easy to understand, and valuable for patients, caregivers, medical students, and healthcare professionals alike.

What is Hereditary Haemochromatosis (HFE)?

Hereditary Haemochromatosis (HFE) is a genetic disorder characterized by excessive absorption of dietary iron from the intestine. Unlike most individuals, whose bodies carefully regulate iron levels, people with this condition absorb more iron than needed. Since the body has no natural mechanism to excrete excess iron efficiently, it accumulates over years or decades.

The term haemochromatosis comes from Greek words meaning blood color, reflecting the deep pigmentation changes that can occur in advanced disease due to iron deposition in the skin.

HFE-related haemochromatosis is primarily caused by mutations in the HFE gene, most commonly the C282Y mutation. This genetic alteration disrupts normal iron regulation, leading to iron overload.

Key Facts About Hereditary Haemochromatosis

• It is one of the most common genetic disorders in people of European descent.
• It affects men more severely than women, as women lose iron through menstruation.
• Symptoms often appear between 30 and 60 years of age.
• If detected early, the condition is highly treatable and complications can be prevented.
• If left untreated, it can cause liver cirrhosis, diabetes, heart disease, and joint damage.

Genetic Cause: The HFE Gene Mutation

Hereditary Haemochromatosis is most commonly associated with mutations in the HFE gene located on chromosome 6. The HFE gene plays a crucial role in regulating how much iron the body absorbs from food.

The two most important mutations in this gene are:

• C282Y mutation – The most common and clinically significant mutation.
• H63D mutation – Less severe but can contribute to iron overload in combination with C282Y.

Individuals who inherit two copies of the C282Y mutation (one from each parent) are at the highest risk of developing iron overload. Those with one copy (carriers) usually do not develop severe disease but may have mildly elevated iron levels.

Important Genetic Insight: Not everyone with HFE mutations develops clinical haemochromatosis. Environmental factors, diet, alcohol intake, and other genetic modifiers also play a role.

How Does Iron Overload Affect the Body?

Iron is an essential mineral required for oxygen transport, energy production, and cellular function. However, too much iron is toxic. Excess iron generates free radicals, which damage cells, tissues, and organs.

Over time, iron accumulates in:

• Liver – Leading to fibrosis, cirrhosis, and liver cancer.
• Heart – Causing arrhythmias and cardiomyopathy.
• Pancreas – Resulting in diabetes (bronze diabetes).
• Joints – Leading to arthritis and chronic pain.
• Skin – Causing a bronze or grey discoloration.

Signs and Symptoms of Hereditary Haemochromatosis

Early symptoms are often vague and can be mistaken for common conditions. Many people remain asymptomatic for years.

Early Symptoms

• Fatigue and weakness
• Joint pain, especially in fingers and knees
• Abdominal pain
• Loss of libido
• Depression or mood changes

Advanced Symptoms (If Untreated)

• Liver cirrhosis
• Diabetes
• Heart failure
• Irregular heartbeat
• Skin darkening
• Severe joint damage
• Increased risk of liver cancer

Why Symptoms Differ Between Men and Women?

Men are more likely to develop symptoms earlier because they do not lose iron through menstruation. Women typically present symptoms after menopause when iron begins to accumulate more rapidly.

How is Hereditary Haemochromatosis Diagnosed?

Early diagnosis is crucial to prevent organ damage. The diagnostic process involves a combination of blood tests, genetic testing, and sometimes imaging or liver biopsy.

1. Blood Tests

Doctors usually start with two key tests:

• Serum Ferritin – Measures stored iron in the body.
• Transferrin Saturation (TSAT) – Indicates how much iron is bound to transferrin.

Elevated ferritin and transferrin saturation levels strongly suggest iron overload.

2. Genetic Testing (HFE Mutation Test)

If blood tests indicate iron overload, genetic testing is performed to confirm the presence of C282Y or H63D mutations.

3. Imaging and Liver Assessment

In severe cases, doctors may order:

• MRI of the liver to assess iron deposition
• Liver biopsy (rarely, only in advanced cases)

Test	Purpose
Serum Ferritin	Measures total body iron stores
Transferrin Saturation	Shows circulating iron level
HFE Genetic Test	Confirms mutation
MRI Liver	Detects iron accumulation

Treatment of Hereditary Haemochromatosis

The good news is that Hereditary Haemochromatosis is highly treatable, especially when diagnosed early.

1. Therapeutic Phlebotomy (Blood Removal)

This is the most common and effective treatment. It involves regularly removing blood from the body, similar to blood donation. This helps reduce iron levels gradually.

• Initially: Weekly phlebotomy for several months
• Maintenance phase: Every 2–4 months

Most patients feel significantly better after iron levels normalize.

2. Iron Chelation Therapy

For patients who cannot undergo phlebotomy (e.g., anemia or heart disease), medications like deferoxamine may be used to bind excess iron and remove it through urine or stool.

3. Dietary Modifications

While diet alone cannot cure haemochromatosis, it can help manage iron levels.

Foods to Limit

• Red meat
• Liver and organ meats
• Iron-fortified cereals
• Vitamin C supplements (increase iron absorption)
• Alcohol (especially harmful to the liver)

Foods Recommended

• Tea and coffee (reduce iron absorption)
• Calcium-rich foods
• Whole grains and vegetables

Note: Never stop prescribed treatment without consulting a doctor.

Complications of Untreated Haemochromatosis

If left untreated, iron overload can lead to serious complications such as:

• Liver cirrhosis and liver cancer
• Heart disease and arrhythmias
• Type 2 diabetes
• Severe arthritis
• Hypothyroidism
• Infertility in men

Early detection can prevent most of these complications.

Who Should Get Tested?

Genetic testing is recommended for:

• People with a family history of haemochromatosis
• Individuals with unexplained high ferritin levels
• Those with symptoms such as fatigue, joint pain, or liver problems
• Siblings, children, or parents of diagnosed patients

Living with Hereditary Haemochromatosis

With proper treatment and lifestyle changes, most people with haemochromatosis can live a normal, healthy life.

Key Lifestyle Tips

• Follow regular phlebotomy schedule
• Avoid excessive alcohol
• Maintain a balanced diet
• Regular monitoring of ferritin levels
• Annual liver function tests

Myths vs Facts

Common Myths

• Myth: Haemochromatosis is rare. Fact: It is one of the most common genetic disorders.
• Myth: Only men get it. Fact: Women can also develop it, especially after menopause.
• Myth: Diet alone can cure it. Fact: Phlebotomy is the main treatment.

Conclusion

Hereditary Haemochromatosis (HFE) is a serious but manageable genetic condition. The key to a healthy life lies in early diagnosis, regular monitoring, and proper treatment. If you or someone in your family has a history of iron overload, genetic testing and medical consultation are highly recommended.

With modern medical care, individuals with haemochromatosis can prevent complications and maintain a good quality of life. Awareness, timely testing, and proactive management are the most powerful tools against this condition.

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