Molecular analyses of patients with hyperferritinemia and normal serum iron values reveal both L ferritin IRE and 3 new ferroportin (slc11A3) mutations

Blood. 2003 Sep 1;102(5):1904-10. doi: 10.1182/blood-2003-02-0439. Epub 2003 May 1.


Unexplained hyperferritinemia is a common clinical finding, even in asymptomatic persons. When early onset bilateral cataracts are also present, the hereditary hyperferritinemia-cataract syndrome (HHCS), because of heterozygous point mutation in the L ferritin iron-responsive element (IRE) sequence, can be suspected. We sequenced the L ferritin exon 1 in 52 DNA samples from patients referred to us for molecular diagnosis of HHCS. We identified 24 samples with a point mutation/deletion in the IRE. For the 28 samples in which no IRE mutation was present, we also genotyped HFE mutations and sequenced both H ferritin and ferroportin genes. We found an increased frequency of His63Asp heterozygotes (12 of 28) but no H ferritin mutations. We identified 3 new ferroportin mutations, producing, respectively, Asp157Gly, Gln182His, and Gly323Val amino acid replacements, suggesting that these patients have dominant type 4 hemochromatosis. This study demonstrates that both L ferritin IRE and ferroportin mutations can account for isolated hyperferritinemia. The presence of cataract does not permit the unambiguous identification of patients with HHCS, although the existence of a family history of cataract was only encountered in these patients. This raises the intriguing possibility that lens ferritin accumulation might be a factor contributing to age-related cataract in the general population. Additional causes of isolated hyperferritinemia remain to be identified.

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Apoferritins
  • Cataract / genetics
  • Cataract / metabolism
  • Cation Transport Proteins / genetics*
  • Cation Transport Proteins / metabolism
  • Child
  • Child, Preschool
  • Female
  • Ferritins / blood*
  • Gene Deletion
  • Humans
  • Iron / blood
  • Iron Metabolism Disorders / blood*
  • Iron Metabolism Disorders / genetics*
  • Iron Regulatory Protein 1 / genetics*
  • Iron Regulatory Protein 1 / metabolism
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Point Mutation


  • Cation Transport Proteins
  • metal transporting protein 1
  • Ferritins
  • Apoferritins
  • Iron
  • Iron Regulatory Protein 1