Haemochromatosis

Introduction

Haemochromatosis is a condition characterised by excessive accumulation of iron in the body, leading to iron deposition in various tissues and resultant organ damage. It can be classified into:

• Primary (Hereditary) Haemochromatosis – Most commonly due to mutations in the HFE gene, inherited in an autosomal recessive pattern.
• Secondary Haemochromatosis – Caused by external factors such as repeated blood transfusions (e.g. in beta-thalassaemia major), chronic liver disease, excessive iron intake, or ineffective erythropoiesis.

Peak Incidence

• Typically presents between 30 and 50 years of age.
• Men are more likely to be symptomatic earlier due to the absence of regular physiological iron loss (e.g. menstruation or pregnancy).

Pathophysiology

• In hereditary haemochromatosis, HFE gene mutations (commonly C282Y and H63D) impair the regulation of iron absorption in the gut.
• This leads to increased intestinal iron absorption and progressive iron overload, with eventual deposition in the liver, pancreas, heart, joints, skin, and endocrine glands.

Symptoms

General

• Fatigue and lethargy
• Reduced libido
• Non-specific early symptoms, often delaying diagnosis

Skin

• Hyperpigmentation, giving a bronze or slate-grey skin tone

Signs

Liver

• Hepatomegaly
• Right upper quadrant discomfort
• Progression to cirrhosis

Pancreas

• Diabetes mellitus (often referred to as “bronze diabetes” when associated with skin pigmentation)

Joints

• Arthralgia, particularly in the second and third metacarpophalangeal (MCP) joints
• Chondrocalcinosis

Heart

• Cardiomyopathy (dilated or restrictive)
• Arrhythmias, such as atrial fibrillation

Diagnosis

Blood Tests

• Serum ferritin – Raised; indicates iron overload but may be elevated in inflammatory states
• Transferrin saturation – Typically ≥45%; more specific marker of iron overload
• Serum iron and TIBC – High serum iron with low total iron-binding capacity

Genetic Testing

• Confirmatory testing for HFE gene mutations (most commonly C282Y homozygosity)

Imaging

• MRI of the liver – Non-invasive method to assess hepatic iron concentration
• Cardiac MRI or echocardiography – Performed if cardiac involvement is suspected

Liver Biopsy

• Previously used to assess iron load and fibrosis; now less common due to MRI and genetic testing
• If performed, Prussian blue stain highlights iron accumulation in hepatocytes

Complications

• Cirrhosis – From chronic iron-induced liver injury
• Cardiomyopathy – Often dilated, may be reversible with early treatment
• Diabetes mellitus – Due to pancreatic islet cell damage
• Arthropathy – Permanent joint damage
• Hepatocellular carcinoma – Increased risk in patients with cirrhosis
• Endocrine dysfunction – Including hypogonadism, adrenal insufficiency, and hypothyroidism

Management

Lifestyle Modifications

• Avoid alcohol to reduce hepatic injury
• Avoid excessive vitamin C intake, which enhances iron absorption
• Offer genetic counselling to family members of affected individuals

Primary Treatment: Therapeutic Phlebotomy (Venesection)

• Initial phase – Weekly blood removal to reduce iron stores
• Maintenance phase – Periodic removal (typically 3–4 times per year) to maintain normal iron levels

Iron Chelation Therapy

• Used if phlebotomy is contraindicated (e.g. in anaemia)
• Example: Deferoxamine

Advanced Disease Management

• Liver transplantation may be necessary in cases of liver failure or hepatocellular carcinoma