Treatment for H63D Hemochromatosis
Therapeutic phlebotomy is the mainstay of treatment for H63D hemochromatosis with confirmed iron overload, with a target ferritin level of 50-100 μg/L. 1, 2
Diagnosis Confirmation Before Treatment
Before initiating treatment, confirm iron overload with:
- Elevated serum ferritin (>200 μg/L in women, >300 μg/L in men)
- Elevated transferrin saturation (>45% in women, >50% in men)
- Genetic testing confirming H63D mutation
Important: H63D heterozygotes generally have a much lower risk of developing clinically significant iron overload compared to C282Y homozygotes 2. Treatment should only be initiated if there is laboratory-confirmed iron overload.
Treatment Protocol
Initial Iron Depletion Phase
- Weekly or biweekly phlebotomy (removal of 450-500 mL blood) 1, 2
- Check hemoglobin/hematocrit before each phlebotomy
- Ensure hemoglobin/hematocrit does not fall by more than 20% of prior level
- Monitor serum ferritin every 10-12 phlebotomies (approximately every 3 months)
- Continue until serum ferritin reaches 50-100 μg/L
Maintenance Phase
- After achieving target ferritin levels, transition to maintenance phlebotomy
- Frequency varies based on individual iron reaccumulation rates:
- Some patients require monthly phlebotomy
- Others may need only 1-2 units removed per year
- Regular monitoring of ferritin levels to guide frequency
Special Considerations
Monitoring
- Regular liver function tests to detect liver disease
- Consider MRI quantification of liver iron in cases where diagnosis is equivocal
- Consider liver biopsy if ferritin >1000 μg/L, elevated liver enzymes, or age >40 years
Adjunctive Measures
- Avoid vitamin C supplements during active iron reduction therapy (increases iron toxicity) 1, 2
- Avoid iron supplements
- Avoid raw shellfish (risk of Vibrio vulnificus infection)
- No specific dietary restrictions are necessary as dietary iron absorption (2-4 mg/day) is minimal compared to phlebotomy removal (250 mg/week) 1
- Limit alcohol consumption
Alternative Treatment Options
- For patients who cannot tolerate phlebotomy, erythroapheresis may be considered as it can remove excess iron twice as fast as manual whole blood phlebotomy 3
- Iron chelation therapy is generally reserved for secondary iron overload conditions rather than hereditary hemochromatosis
Expected Outcomes
Successful treatment can lead to:
- Normalization of elevated liver enzymes
- Reduction in skin pigmentation
- Possible reversal of hepatic fibrosis (in approximately 30% of cases)
- Elimination of risk of hemochromatosis-related hepatocellular carcinoma if iron removal is achieved before development of cirrhosis
- Reduction in portal hypertension in patients with cirrhosis
Note that established cirrhosis is not reversible with iron removal, and arthropathy typically shows minimal improvement despite treatment 1.
Pitfalls and Caveats
- H63D heterozygotes rarely develop significant iron overload unless other contributing factors are present (alcohol use, metabolic syndrome, etc.) 2, 4
- Avoid inducing iron deficiency through excessive phlebotomy
- In patients with cardiac involvement, more careful monitoring is required during phlebotomy due to risk of arrhythmias with rapid iron mobilization 1, 2
- Consider screening first-degree relatives of patients with confirmed hemochromatosis 2