Haemochromatosis is a genetic disorder characterised by excessive iron absorption and accumulation in tissues, leading to organ damage. Early diagnosis and treatment can prevent complications.

Aetiology:

1. Primary (Hereditary Haemochromatosis):
   • Autosomal recessive mutation in the HFE gene (most commonly C282Y mutation).
   • Increased intestinal iron absorption.
2. Secondary (Acquired):
   • Chronic transfusions (e.g., in thalassaemia or sickle cell disease).
   • Chronic liver disease (e.g., alcoholic liver disease, chronic hepatitis B/C).

Pathophysiology:

• Excessive iron absorption from the gastrointestinal tract.
• Iron accumulates in tissues (e.g., liver, heart, pancreas), causing oxidative damage.

Clinical Features:

1. General Symptoms:
   • Fatigue, arthralgia, lethargy.
2. Specific Signs:
   • Skin: Hyperpigmentation (“bronze diabetes”).
   • Liver: Hepatomegaly, cirrhosis, risk of hepatocellular carcinoma.
   • Pancreas: Diabetes mellitus (secondary to iron-induced beta-cell damage).
   • Heart: Cardiomyopathy, arrhythmias, heart failure.
   • Joints: Arthropathy (especially of the 2nd and 3rd metacarpophalangeal joints).
   • Hypogonadism: Testicular atrophy, impotence, amenorrhoea.

Investigations:

1. Blood Tests:
   • Serum Ferritin: Elevated (indicates total iron stores).
   • Transferrin Saturation: Elevated (>45% confirms iron overload).
   • Serum Iron: Elevated.
2. Genetic Testing:
   • HFE gene mutation analysis (e.g., C282Y homozygous or C282Y/H63D compound heterozygous).
3. Imaging:
   • Liver MRI: Assesses iron deposition.
4. Liver Biopsy (if needed):
   • Confirms iron overload and assesses fibrosis or cirrhosis.
5. Specialist Tests:
   • Echocardiogram and ECG for cardiac involvement.
   • Blood glucose levels for diabetes screening.

Management:

1. Lifestyle Changes:
   • Avoid iron and vitamin C supplements (vitamin C increases iron absorption).
   • Limit alcohol intake to reduce liver damage.
2. Therapeutic Phlebotomy (First-Line):
   • Regular removal of blood to lower iron levels.
   • Target ferritin: 50–100 µg/L.
   • Frequency: Weekly initially, then maintenance every 2–3 months.
3. Iron Chelation Therapy:
   • For patients who cannot tolerate phlebotomy (e.g., anaemia or secondary haemochromatosis).
   • Agents: Deferasirox, Deferoxamine.
4. Monitoring and Treating Complications:
   • Regular screening for hepatocellular carcinoma (HCC) in cirrhotic patients.
   • Treat diabetes, cardiomyopathy, or endocrine dysfunctions as needed.

Complications:

1. Liver:
   • Cirrhosis, hepatocellular carcinoma.
2. Cardiovascular:
   • Dilated cardiomyopathy, arrhythmias.
3. Endocrine:
   • Diabetes mellitus, hypogonadism.
4. Joint:
   • Chronic arthropathy.
5. Infection:
   • Increased susceptibility to infections (e.g., Listeria, Yersinia, Vibrio vulnificus).

Prognosis:

• Excellent if diagnosed early and treated before organ damage occurs.
• Reduced life expectancy if complications like cirrhosis or cardiomyopathy develop.

Key Exam Points for UKMLA:

1. Genetics:
   • Autosomal recessive condition; C282Y mutation is the most common.
2. Diagnosis:
   • Elevated serum ferritin and transferrin saturation; confirm with genetic testing.
3. Management:
   • Therapeutic phlebotomy is first-line; consider iron chelation if contraindicated.
4. Complications:
   • Be aware of liver cirrhosis, diabetes, and cardiac involvement.
5. Prevention:
   • Early screening in at-risk individuals (e.g., family history).