What is the best treatment for a 65-year-old male with HFE C282Y mutation and normal hemoglobin (Hb) level due to hereditary hemochromatosis?

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Treatment for 65-Year-Old Male with HFE C282Y Homozygosity and Hemoglobin 17.5

This patient requires therapeutic phlebotomy if he has elevated serum ferritin levels, regardless of symptoms, as early treatment before cirrhosis or diabetes develops ensures normal survival. 1

Initial Assessment Required

Before initiating treatment, you must determine the extent of iron overload and assess for liver disease:

  • Measure serum ferritin and transferrin saturation immediately 1
  • Check liver enzymes (ALT, AST) and platelet count 1
  • If ferritin >1000 µg/L OR elevated liver enzymes are present, perform liver biopsy to stage fibrosis and assess for cirrhosis 1
    • Ferritin <1000 µg/L accurately predicts absence of cirrhosis 1
    • At age 65, this patient is at higher risk for advanced fibrosis and should have biopsy if ferritin is elevated with abnormal liver enzymes 1

Treatment Algorithm Based on Findings

If Ferritin is Elevated (Above Normal Range)

Initiate therapeutic phlebotomy immediately 1:

  • Remove 500 mL of blood (1 unit) weekly until ferritin normalizes 1
  • Each unit removes approximately 200-250 mg of iron 1
  • Continue weekly phlebotomy during "de-ironing" phase 1
  • Once ferritin reaches 50-100 µg/L, transition to maintenance phlebotomy (typically every 2-4 months) 1

If Ferritin is Normal

  • Monitor with annual serum ferritin and transferrin saturation 1
  • Initiate phlebotomy if ferritin rises above normal range 1

Expected Treatment Outcomes

Phlebotomy before cirrhosis develops provides excellent results 1:

  • Malaise, fatigue, skin pigmentation, and abdominal pain respond well to treatment 1
  • Insulin requirements for diabetics improve 1
  • Hepatic fibrosis may reverse in approximately 30% of cases 1
  • Survival normalizes if treatment begins before cirrhosis or diabetes 1, 2

Poor Response Features

  • Arthropathy and hypogonadism show minimal or no improvement 1
  • Established cirrhosis does not reverse 1
  • If cirrhosis is present, continue lifelong surveillance for hepatocellular carcinoma even after successful iron depletion 1

Critical Pitfalls to Avoid

Do not delay treatment waiting for symptoms to develop 1. The hemoglobin of 17.5 g/dL is actually elevated (likely secondary polycythemia from iron overload effects), not a contraindication to phlebotomy. This makes phlebotomy even more appropriate as it will address both the iron overload and the elevated hemoglobin 1.

Do not assume this patient is asymptomatic without specific questioning 1. Ask specifically about:

  • Fatigue and malaise
  • Joint pain (especially metacarpophalangeal joints)
  • Abdominal pain
  • Sexual dysfunction
  • Skin changes 1

At age 65 with C282Y homozygosity, assume significant iron accumulation has occurred 1. The critical window for preventing irreversible organ damage may be closing, making prompt evaluation and treatment essential 1, 2.

If cirrhosis is found on biopsy, the risk of hepatocellular carcinoma remains elevated (30% of HH-related deaths) even with successful phlebotomy 1. These patients require ongoing HCC surveillance with imaging every 6 months 1.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

HFE Gene Mutation and Hereditary Hemochromatosis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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