What is the best course of action to increase ferritin levels to at least 70 in a patient with one copy of the C282Y variant, negative for the H63D variant, and currently taking iron supplements, with lab results showing ferritin at 52, iron at 126, iron binding capacity at 256, and iron saturation at 49%?

Management Recommendation for Iron Supplementation in C282Y Heterozygote

Continue the current iron supplementation regimen to achieve the target ferritin of 70 ng/mL, as this patient has no risk of clinically significant iron overload from her C282Y heterozygous genotype. 1, 2

Genetic Context and Iron Overload Risk

This patient's genetic profile carries no meaningful risk for hereditary hemochromatosis or iron overload:

• C282Y heterozygotes do not develop iron overload unless a second mutation (such as H63D compound heterozygosity) or significant cofactor (chronic liver disease, alcohol abuse) is present 1, 2
• A prospective 12-year study of 257 C282Y heterozygotes showed no documented iron overload in any simple heterozygote, with mean transferrin saturation remaining stable and similar to wild-type controls 2
• The American Association for the Study of Liver Diseases confirms that C282Y heterozygotes can be reassured they are not at risk for developing progressive or symptomatic iron overload 1

Current Iron Status Assessment

Her iron parameters reveal functional iron deficiency despite the elevated iron saturation:

• Ferritin 52 ng/mL is below the target of 70 ng/mL and indicates depleted iron stores 1
• The iron saturation of 49% is artificially elevated because the blood draw occurred only 72 hours after her last iron dose, and iron parameters should not be evaluated within 4 weeks of iron supplementation as circulating iron interferes with assays 1
• Her calculated TIBC of 256 mg/dL with serum iron of 126 mg/dL confirms the 49% saturation, but this measurement is unreliable given recent iron intake 1

Recommended Management Plan

Continue Current Iron Supplementation

• Maintain the current regimen of two iron capsules every Monday, Wednesday, and Friday 3
• The goal is to achieve ferritin ≥70 ng/mL, and she has not yet reached this target 1
• Continue supplementation for at least 3 months to fully replenish iron stores, not just until ferritin normalizes 1

Proper Laboratory Monitoring

• Recheck ferritin and transferrin saturation 4-8 weeks after the last iron dose to allow accurate assessment without interference from circulating supplemental iron 1
• Patients should avoid all iron supplements for at least 24 hours (ideally 4 weeks) before blood draw for accurate iron studies 1
• The morning fasting sample is preferred for transferrin saturation measurement 1

Expected Response

• Hemoglobin should increase by 1-2 g/dL within 4-8 weeks of continued therapy 1
• Ferritin should rise progressively toward the target of ≥70 ng/mL 1
• Once ferritin reaches ≥70 ng/mL, continue supplementation to maintain levels between 50-100 ng/mL 1

Critical Pitfalls to Avoid

• Do not discontinue iron supplementation based on the elevated transferrin saturation of 49%, as this value is spuriously elevated from recent iron intake and does not reflect true iron overload 1
• Do not pursue phlebotomy or iron reduction therapy in C282Y heterozygotes, as they do not develop clinically significant iron accumulation 1, 2
• Never interpret transferrin saturation within 4 weeks of iron supplementation, as the test becomes unreliable 1
• Do not assume iron overload risk from C282Y heterozygosity alone—this genotype requires a second genetic hit or significant cofactor to cause disease 1, 2

Patient Counseling Points

• Reassure the patient that her genetic variant does not increase risk of iron overload and she can safely continue iron supplementation to correct her deficiency 1, 2
• Occasional gastrointestinal discomfort may be minimized by taking iron with meals 3
• Iron supplements may occasionally cause constipation or diarrhea 3
• Do not take iron within 2 hours of certain antibiotics, as iron interferes with their absorption 3