What are the diagnostic and treatment approaches for hemochromatosis?

Diagnostic and Treatment Approaches for Hemochromatosis

The primary treatment for hemochromatosis is therapeutic phlebotomy, which should be performed weekly until serum ferritin levels reach 50-100 μg/L, followed by maintenance phlebotomy to keep ferritin in this target range. 1

Diagnosis

Initial Diagnostic Evaluation

• Serum iron studies:

  • Transferrin saturation (TSAT) >45% suggests true iron overload 2
  • Elevated serum ferritin (>300 μg/L in men, >200 μg/L in women) 3
  • Note: Serum ferritin alone is insufficient as it can be elevated in inflammatory conditions without true iron overload 2

• Genetic testing:

  • HFE genotyping for p.C282Y and H63D mutations 2
  • C282Y homozygosity is the most common genetic cause 4
  • Non-HFE forms (mutations in HAMP, HJV, TFR2, or SLC40A1) are much rarer 4

• Additional testing:

  • Liver function tests to assess for hepatic damage 2
  • Screen for inflammatory markers (CRP, ESR) to rule out inflammatory causes of elevated ferritin 2
  • MRI can quantify hepatic iron concentration non-invasively 2

Liver Biopsy Considerations

• Liver biopsy may be needed to:

  • Confirm iron overload in uncertain cases
  • Assess for presence of cirrhosis (affects prognosis and management)
  • Quantify hepatic iron concentration

• When to proceed directly to phlebotomy without liver biopsy:

  • C282Y homozygotes with elevated ferritin <1000 μg/L without indicators of significant liver disease (normal ALT/AST) 1

Treatment

Therapeutic Phlebotomy

• Initial therapy:

  • Remove one unit of blood (450-500 mL) weekly or biweekly 1
  • Check hematocrit/hemoglobin before each phlebotomy
  • Allow hematocrit/hemoglobin to fall by no more than 20% of prior level 1
  • Check serum ferritin every 10-12 phlebotomies (approximately every 3 months) 1

• Target levels:

  • Continue frequent phlebotomy until serum ferritin reaches 50-100 μg/L 1
  • Then transition to maintenance phlebotomy

• Maintenance therapy:

  • Frequency varies among individuals based on rate of iron reaccumulation
  • Some patients require monthly phlebotomy, others only 1-2 units per year 1
  • Continue to maintain serum ferritin between 50-100 μg/L 1

Iron Chelation Therapy

• Indications:

  • Secondary iron overload due to dyserythropoiesis 1
  • Patients who cannot tolerate phlebotomy

• Options:

  • Deferasirox (oral): Requires close monitoring for renal failure, hepatic failure, and gastrointestinal hemorrhage 5
  • Deferoxamine (parenteral): 20-40 mg/kg body weight per day 1

Dietary and Lifestyle Recommendations

• Avoid:

  • Vitamin C supplements (accelerate iron mobilization) 1
  • Iron supplements 2
  • Raw shellfish (risk of Vibrio vulnificus infection) 1

• Consider:

  • Weight loss if overweight/obese 2
  • Limited alcohol intake or abstinence 2
  • Reduced consumption of processed foods and sugar 2

Monitoring

• During initial treatment:

  • Hematocrit/hemoglobin prior to each phlebotomy 1
  • Serum ferritin every 10-12 phlebotomies 1
  • Liver enzymes to detect liver damage 2

• Long-term monitoring:

  • Regular assessment of serum ferritin and transferrin saturation (every 1-3 months during active treatment) 2
  • Screen for complications: diabetes, arthropathy, cardiac dysfunction 2
  • Consider follow-up liver biopsy to confirm adequate iron removal in severe cases 1

Special Considerations

Patients with Advanced Disease

• Patients with advanced cirrhosis may need liver transplantation 1
• Cardiac complications require careful monitoring during phlebotomy due to risk of sudden death with rapid iron mobilization 1

Complications to Monitor

• Hepatic cirrhosis and hepatocellular carcinoma
• Diabetes mellitus
• Hypogonadism
• Arthropathy
• Cardiomyopathy and arrhythmias

Common Pitfalls

• Overlooking the diagnosis: Hemochromatosis is often underdiagnosed despite being a common genetic disorder 6
• Relying solely on serum ferritin: Must combine with transferrin saturation for accurate diagnosis 7
• Confusing secondary iron overload with hemochromatosis: Consider alcohol use, chronic hepatitis, and other causes of elevated ferritin 2
• Excessive phlebotomy: Avoid causing iron deficiency (ferritin <50 μg/L) 1
• Inadequate monitoring: Regular follow-up is essential to prevent complications 1