STEP

ACTION UNDERTAKEN

1

Basic biology and clinical examination

  • Hyperferritinemia in an adult (male >300µg/L, female >200µg/L)
  • High transferring saturation (male >60%, female > 50%)
  • Exclude acquired causes: hematologic disorder, alcohol, cell necrosis

2

Basic genetic testing

  • Test HFE (C282Y)
    • C282Y homozygote: HFE hemochromatosis stop (unless very severe iron overload, follow step 4-2)
    • C282Y heterozygote
      • Test HFE (H63D)
        • C282Y/H63D compound heterozygote + mild iron overload: stop
        • C282Y/H63D compound heterozygote + high iron parameters: follow step 3
        • No H63D: follow step 3
    • Other HFE genotypes: follow step 3

3

Quantification of hepatic iron (magnetic resonance Imaging or liver biopsy)

  1. HII ≤1.9 µmol/g/year:STOP
  2. HII >1.9 µmol/g/year:follow step 4

4

Specialized genetic testing

  • Sequence the HFE gene:
  • Presence of a private HFE mutation (can explain iron overload)
  • No additional HFE mutation: sequence iron-related genes (HAMP, HFE2/HJV, TFR2, SLC40A1)
Table 5: Step strategy for the diagnosis of rare HFE mutations associated with C282Y in a compound heterozygous state [14].