Genotypic/phenotypic correlations in genetic hemochromatosis: evolution of diagnostic criteria

Gastroenterology. 1998 Feb;114(2):319-23. doi: 10.1016/s0016-5085(98)70483-4.


Background & aims: The identification of a candidate gene for hereditary hemochromatosis in 69%-100% of patients with hemochromatosis has resulted in a diagnostic genotypic test (C282Y). The aim of this study was to reassess the phenotypic diagnostic criteria for hemochromatosis in patients homozygous for the C282Y mutation of the HFE gene.

Methods: Transferrin saturation, ferritin, hepatic iron index, and iron removed by venesection were studied in C282Y++ homozygotes and C282Y-- putative homozygotes.

Results: Patients were homozygous for the C282Y mutation in 122 of 128 cases (95%). In C282Y homozygotes, the results were as follows: hepatic iron index, >1.9 in 91.3%; transferrin saturation, >55% in 90%; serum ferritin, >300 microg/L in 96% of men and >200 microg/L in 97% of women; and iron removed, >5 g in 70% of men and 73% of women. There were four homozygotes for C282Y with no biochemical evidence of iron overload.

Conclusions: The sensitivity of the phenotypic tests in decreasing order was as follows: serum ferritin, hepatic iron index, transferrin saturation, and iron removed by venesection. Although the genetic test is useful in the diagnostic algorithm, this study has shown both iron-loaded patients without the mutation and homozygous patients without iron overload.

MeSH terms

  • Adult
  • Aged
  • Female
  • Ferritins / blood
  • HLA Antigens / genetics
  • Hemochromatosis / blood
  • Hemochromatosis / diagnosis
  • Hemochromatosis / genetics*
  • Hemochromatosis Protein
  • Heterozygote
  • Histocompatibility Antigens Class I / genetics
  • Homozygote*
  • Humans
  • Iron / analysis
  • Liver / chemistry
  • Male
  • Membrane Proteins*
  • Middle Aged
  • Mutation / genetics*
  • Phenotype
  • Sex Factors


  • HFE protein, human
  • HLA Antigens
  • Hemochromatosis Protein
  • Histocompatibility Antigens Class I
  • Membrane Proteins
  • Ferritins
  • Iron