Hereditary Hemochromatosis (HH) is a genetic disorder characterized by excessive absorption of dietary iron, leading to iron overload in vital organs such as the liver, heart, pancreas, and joints. Over time, this iron accumulation can cause severe complications, including cirrhosis, diabetes, heart disease, and arthritis.
While HH is one of the most common genetic disorders in people of European descent, many individuals remain undiagnosed due to its often subtle and nonspecific symptoms. Early detection and treatment are crucial in preventing long-term complications.
In this blog, we will explore the causes, symptoms, diagnosis, and management of hereditary hemochromatosis.
What is Hereditary Hemochromatosis?
Hereditary Hemochromatosis (HH) is an inherited disorder that disrupts the body’s ability to regulate iron absorption. Normally, the body absorbs only as much iron as it needs from food, but in HH, excess iron is absorbed and stored in organs, leading to toxicity.
Types of Hereditary Hemochromatosis
There are four main types of hereditary hemochromatosis:
- Type 1 (Classic HH) – The most common form, caused by mutations in the HFE gene.
- Type 2 (Juvenile HH) – A rare and severe form that appears in early life, caused by mutations in the HJV or HAMP genes.
- Type 3 (Intermediate HH) – Affects adults but is less common than Type 1, caused by TFR2 gene mutations.
- Type 4 (Ferroportin Disease) – A unique form caused by mutations in the SLC40A1 gene, leading to iron buildup in macrophages rather than organs.
Causes of Hereditary Hemochromatosis
HH is caused by genetic mutations that affect the regulation of iron absorption. The most common mutation occurs in the HFE gene, specifically the C282Y and H63D variants.
How Does the Mutation Cause Iron Overload?
- The HFE gene normally helps regulate iron absorption in the intestines.
- When mutated, it disrupts the body’s iron-sensing mechanisms.
- This leads to increased absorption of iron from food, even when the body has sufficient iron stores.
- Excess iron gets deposited in various organs, leading to damage over time.
Inheritance Pattern
HH follows an autosomal recessive inheritance pattern, meaning a person needs to inherit two mutated copies of the gene (one from each parent) to develop the disease. However, individuals with only one mutation (carriers) may still have mild iron overload.
Hereditary Hemochromatosis symptoms
Symptoms of HH vary and often develop gradually over decades. In many cases, symptoms do not appear until middle age (40–60 years in men, postmenopausal in women) because menstruation and pregnancy help women lose excess iron naturally.
Early Symptoms:
Advanced Symptoms:
If untreated, iron overload can lead to severe complications, including:
- Liver Disease – Cirrhosis, fibrosis, liver cancer, and chronic liver disease.
- Diabetes (Bronze Diabetes) – Iron accumulation in the pancreas affects insulin production.
- Heart Problems – Cardiomyopathy, arrhythmias, congestive heart failure.
- Joint Issues (Arthropathy) – Arthritis, particularly in the fingers, hips, and knees.
- Hypogonadism – Iron buildup in the pituitary gland can cause reduced testosterone levels, infertility, and erectile dysfunction in men.
- Skin Changes – Increased skin pigmentation (bronzing) due to iron deposition in the skin.
Diagnosis of Hereditary Hemochromatosis
HH is often underdiagnosed, as its symptoms mimic other common conditions. However, specific tests can help confirm the diagnosis.
1. Blood Tests
- Serum Ferritin – Measures stored iron levels. High levels indicate iron overload.
- Transferrin Saturation (%) – A percentage indicating how much iron is bound to transferrin (a protein that carries iron in the blood). A level above 45% is suggestive of HH.
2. Genetic Testing
- Confirms the presence of HFE gene mutations (C282Y and H63D).
- Recommended for individuals with a family history of HH or abnormal iron studies.
3. Liver Biopsy (For Severe Cases)
- In advanced cases, a biopsy may be needed to assess liver damage (fibrosis or cirrhosis).
- Liver biopsy is now largely replaced by non-invasive imaging techniques.
4. MRI and FibroScan
- MRI T2 (Hepatic Iron Quantification):* Helps measure iron overload in the liver.
- FibroScan: Evaluates liver stiffness to assess cirrhosis or fibrosis.
Hereditary Hemochromatosis treatment
There is no cure for HH, but it can be effectively managed to prevent complications. The primary treatment aims to remove excess iron and prevent further accumulation.
1. Phlebotomy (Blood Removal Therapy)
- The gold standard treatment for HH.
- Similar to blood donation, a set amount of blood is removed at regular intervals.
- Frequency:
- Initially weekly until iron levels normalize.
- Then maintenance phlebotomy every few months.
2. Iron Chelation Therapy
- Used in rare cases where phlebotomy is not feasible (e.g., anemia, heart failure).
- Drugs like deferoxamine, deferasirox, or deferiprone bind excess iron for removal via urine.
3. Lifestyle and Dietary Changes
- Avoid iron-rich foods (e.g., red meat, organ meats, shellfish).
- Limit vitamin C supplements (enhances iron absorption).
- Avoid alcohol (reduces risk of liver damage).
- Avoid raw seafood (reduces the risk of infections like Vibrio vulnificus).
- Consume tea or coffee with meals (helps reduce iron absorption).
4. Monitoring and Long-Term Care
- Regular iron studies and liver function tests.
- Family screening for first-degree relatives.
- Management of complications (e.g., diabetes, liver disease, arthritis).
Complications of Untreated Hemochromatosis
If left untreated, HH can lead to:
- Liver Cirrhosis & Cancer – Increased risk of hepatocellular carcinoma.
- Diabetes – Due to iron deposition in the pancreas.
- Heart Failure & Arrhythmias – Due to iron overload in the myocardium.
- Severe Joint Pain & Arthritis – May require joint replacements.
- Endocrine Disorders – Including hypogonadism and thyroid dysfunction.
Hereditary Hemochromatosis is a common but underdiagnosed genetic disorder that can lead to severe complications if untreated. However, with early detection, regular blood removal, and lifestyle modifications, individuals with HH can lead a normal, healthy life.
If you have a family history of HH or symptoms of iron overload, consult a healthcare provider for screening and genetic testing. Early intervention can prevent long-term organ damage and improve quality of life.
To consult a Doctor or get tested for HH at Sparsh Diagnostic Centre, call our helpline number 9830117733.
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