From the Guidelines
Compound heterozygosity for HHC (hereditary hemochromatosis) requires regular phlebotomy and monitoring to prevent complications like cirrhosis, diabetes, and cardiomyopathy, with target ferritin levels below 50-100 ng/mL, as recommended by the most recent guidelines 1.
Overview of Hereditary Hemochromatosis
Hereditary hemochromatosis is a genetic disorder characterized by excessive iron absorption and accumulation in organs, particularly the liver, heart, and pancreas. Compound heterozygosity occurs when an individual inherits two different mutations in the HFE gene, one from each parent. This condition can lead to iron overload and increase the risk of developing complications like cirrhosis, diabetes, and cardiomyopathy.
Management and Treatment
Management of compound heterozygosity for HHC typically involves regular phlebotomy (blood removal) to reduce iron levels. Initial treatments are often scheduled weekly until iron levels normalize, then maintenance phlebotomies are performed every 2-4 months based on ferritin levels. Patients should monitor serum ferritin and transferrin saturation regularly, with target ferritin levels below 50-100 ng/mL, as recommended by the American Association for the Study of Liver Diseases 1. Dietary modifications include limiting iron-rich foods, avoiding vitamin C supplements with meals, and avoiding alcohol.
Importance of Early Diagnosis and Treatment
Early diagnosis and consistent treatment are essential for preventing organ damage, as the condition progresses slowly but can cause significant health problems if left untreated. The life-threatening complications of established cirrhosis, particularly hepatocellular carcinoma (HCC), continue to be a threat to survival even after adequate phlebotomy. Therefore, patients with cirrhosis should continue to be screened for HCC following phlebotomy, as recommended by the European Association for the Study of the Liver 1.
Key Recommendations
- Regular phlebotomy to reduce iron levels
- Monitoring of serum ferritin and transferrin saturation
- Target ferritin levels below 50-100 ng/mL
- Dietary modifications to limit iron-rich foods and avoid alcohol
- Early diagnosis and consistent treatment to prevent organ damage
By following these recommendations, individuals with compound heterozygosity for HHC can reduce their risk of developing complications and improve their overall quality of life, as supported by the guidelines from the American Association for the Study of Liver Diseases 1 and the European Association for the Study of the Liver 1.
From the Research
Compound Heterozygous for HHC
- Compound heterozygosity for hereditary hemochromatosis (HH) is associated with higher iron stores than C282Y heterozygosity 2
- Serum ferritin levels are significantly higher in female HH heterozygotes, particularly in compound heterozygotes, than in normal women 2
- Mean serum iron and transferrin saturation levels are higher in male and female HH heterozygotes than in normal controls, with the highest levels found in compound heterozygotes 2
- Compound heterozygotes have milder disease than C282Y homozygotes, and clinical signs of HH in these patients are usually associated with other factors such as alcoholism and the dysmetabolic syndrome 3
- The diagnosis of HH is established by genetic testing in patients with elevated transferrin saturation values, and patients with an established diagnosis of HH and iron overload should be treated with phlebotomy to achieve body iron depletion followed by maintenance phlebotomy 3
Treatment and Management
- Phlebotomy is the primary treatment for hereditary hemochromatosis, with the frequency guided by serial measurements of serum ferritin levels and transferrin saturation 4
- Iron chelation therapy, such as deferoxamine (DFO), deferiprone (L1), and the DFO/L1 combination, can be effective in reversing the toxic side effects of iron overload in patients with HH and thalassemia intermedia 5
- Desferrioxamine (DFO) can be an effective alternative therapy for haemochromatosis when phlebotomy is not possible 6