What is the recommended treatment for an individual who is an H63D (hemochromatosis) homozygote?

Treatment of H63D Homozygote Hemochromatosis

For H63D homozygotes, therapeutic phlebotomy is recommended only if iron overload is confirmed by elevated iron studies and MRI or liver biopsy, with a target ferritin level of 50-100 μg/L. 1

Diagnosis and Evaluation

Before initiating treatment, proper evaluation is essential:

1. Iron Studies Assessment:

   • Measure serum transferrin saturation (>45% is more sensitive for early detection) 1
   • Check serum ferritin levels
   • Additional tests: serum iron and total iron binding capacity

2. Confirmation of Iron Overload:

   • MRI to quantify hepatic iron concentration if biochemical evidence exists 1
   • Consider liver biopsy if serum ferritin >1,000 μg/L or liver enzymes are elevated

3. Rule Out Other Causes:

   • Investigate other factors contributing to hyperferritinemia (present in >90% of outpatients) 1:
     • Alcohol consumption
     • Metabolic syndrome/fatty liver disease
     • Inflammation
     • Other genetic factors

Treatment Protocol

Initial Phase

• Weekly or biweekly phlebotomy (removal of 450-500 mL blood) until serum ferritin reaches 50-100 μg/L 2, 1
• Check hematocrit/hemoglobin before each phlebotomy
• Allow hematocrit/hemoglobin to fall by no more than 20% of prior level 2
• Check serum ferritin level every 10-12 phlebotomies 2

Maintenance Phase

• Continue periodic phlebotomy to maintain ferritin between 50-100 μg/L 2, 1
• Typically requires phlebotomy every 2-4 months, but frequency should be individualized based on ferritin reaccumulation rate 1

Important Considerations and Precautions

• Avoid vitamin C supplements during active iron reduction as they can increase iron toxicity 2, 1
• Avoid iron supplements 2, 1
• Avoid raw shellfish due to risk of Vibrio vulnificus infection 2
• Limit alcohol consumption 1
• Manage weight for patients with obesity 1
• No specific dietary adjustments are necessary as the amount of iron absorption affected by diet is small (2-4 mg/day) compared to phlebotomy (250 mg/week) 2

Monitoring

• Monitor serum ferritin and transferrin saturation every 3 months during treatment 1
• Once target ferritin level is reached, adjust to maintenance schedule
• Periodically assess for complications of iron overload:
  • Liver function tests
  • Glucose levels
  • Cardiac function if indicated

Special Considerations

• Advanced cirrhosis is not reversed with iron removal 2
• Phlebotomy has been shown to improve hypertriglyceridemia in HH patients 3
• The severity of iron overload in H63D homozygotes is typically less than in C282Y homozygotes 1, 4
• Some H63D homozygotes may develop significant iron overload requiring treatment 4

Clinical Pitfalls to Avoid

1. Don't assume all H63D homozygotes need treatment - management should be guided by phenotypic presentation and confirmed iron overload, not genotype alone 1

2. Don't overlook other causes of hyperferritinemia - H63D homozygosity often requires additional factors to cause significant iron overload 1, 4

3. Don't continue aggressive phlebotomy without monitoring - excessive phlebotomy can lead to anemia and should be adjusted based on hematocrit/hemoglobin values 2

4. Don't attempt to predict total phlebotomy requirements based solely on initial hepatic iron concentration - individual responses vary significantly 5