Can hemochromatosis be present with an iron saturation of 59% and a ferritin level of 39?

Hemochromatosis Evaluation with 59% Iron Saturation and Low Ferritin

While hemochromatosis is possible with a transferrin saturation of 59% and a ferritin level of 39, this pattern is atypical and suggests either early disease or an alternative diagnosis.

Diagnostic Interpretation

Transferrin saturation (TS) >45% is the primary screening test for hemochromatosis, making the 59% value concerning 1. However, the extremely low ferritin (39) is inconsistent with typical iron overload and requires careful interpretation:

• Transferrin Saturation: 59% exceeds the 55% threshold that suggests increased risk for hemochromatosis and warrants further investigation 2
• Ferritin Level: 39 μg/L is well below the typical range seen in hemochromatosis and actually falls within the iron deficiency range (30-100 μg/L) 1

Possible Explanations

1. Early Hemochromatosis:

   • Early-stage hereditary hemochromatosis can present with elevated transferrin saturation before ferritin rises 2
   • This pattern is sometimes seen in younger patients before significant iron accumulation occurs

2. Non-HFE Hemochromatosis:

   • Rare forms of non-HFE hemochromatosis can present with atypical iron studies 3
   • These include mutations in genes like HJV, HAMP, TFR2, and SLC40A1

3. Mixed Picture:

   • Underlying hemochromatosis with concurrent iron deficiency (e.g., from blood loss)
   • This can mask the typical ferritin elevation seen in hemochromatosis 4

4. Alternative Diagnosis:

   • Dysmetabolic hyperferritinemia can present with variable transferrin saturation 5
   • Hypotransferrinemia due to transferrin gene defects can present with low ferritin and high iron saturation 1

Recommended Approach

1. Confirm Initial Findings:

   • Repeat transferrin saturation test (preferably fasting) to confirm the elevated level 1
   • Recheck ferritin level

2. Genetic Testing:

   • Test for HFE gene mutations (C282Y, H63D) as recommended for patients with elevated transferrin saturation 2, 6
   • Consider expanded genetic testing for non-HFE hemochromatosis if HFE testing is negative 3

3. Evaluate for Concurrent Conditions:

   • Assess for sources of blood loss or other causes of iron deficiency that could explain the low ferritin
   • Check complete blood count and red cell indices for evidence of anemia
   • Consider testing for inflammation (CRP) which can affect iron parameters 1

4. Additional Workup:

   • If genetic testing confirms hemochromatosis, monitor ferritin levels over time to detect rising trends
   • Consider MRI for liver iron quantification if diagnosis remains uncertain 1

Clinical Implications

If hemochromatosis is confirmed despite the low ferritin:

• No immediate therapeutic phlebotomy is needed with ferritin <50 μg/L 1
• Regular monitoring of ferritin and transferrin saturation every 3-6 months is appropriate
• Avoid iron supplementation unless true iron deficiency is confirmed and addressed

Key Pitfalls to Avoid

• Don't dismiss hemochromatosis solely due to low ferritin - transferrin saturation often rises before ferritin in early disease
• Don't initiate phlebotomy with such low ferritin levels - this could worsen potential iron deficiency 4
• Don't assume all elevated transferrin saturation indicates hemochromatosis - other conditions can cause this pattern

Remember that the combination of elevated transferrin saturation with low ferritin is unusual and warrants thorough investigation before establishing a definitive diagnosis.