Hereditary hyperferritinemia-cataract syndrome in two large multigenerational American families

Julia Shekunov, Piet C. De Groen, Noralane M. Lindor, George G. Klee, Ross A. Aleff, Eric D. Wieben, Brian G. Mohney

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Purpose: Hereditary hyperferritinemia cataract syndrome (HHCS), an autosomal-dominant disorder characterized by hyperferritinemia and bilateral cataracts, is caused by mutations in the iron-responsive element of the ferritin light chain (FTL) gene. The purpose of this study is to describe the genotypic and phenotypic manifestations of HHCS observed in 2 large sets of unrelated American families. Methods: Forty-five patients were recruited from 2 unrelated families. Each underwent ophthalmological and general physical evaluation as well as laboratory testing of serum ferritin, iron, transferrin saturation, and total iron binding capacity. Serum DNA was evaluated for mutations by DNA amplification and sequencing of the FTL gene. Results: Numerous cortical and nuclear white opacities in a stellate pattern occurred in 22 affected individuals and were the only clinical manifestation of HHCS. Of the 22, 16 (73%) demonstrated >1.00 D of astigmatism. Genetic analysis revealed mutation G32A in Pedigree 1 and mutation G32T in Pedigree 2, both heterozygous and located in the iron-responsive element of the ferritin light chain mRNA. Serum ferritin levels of affected subjects ranged from 555 to 2,453 μg/L (normal range, 24-336 μg/L male, 11-307 μg/L female), with greater ferritin levels and more severe cataracts associated with mutation G32A. Conclusions: Most clinical and genetic findings from these families are consistent with previous reports of HHCS. Astigmatism, previously not associated with HHCS, was present in the majority. Ferritin levels and age of cataract surgery varied among subjects with both FTL gene mutations, suggesting that phenotypic variability is modulated by other genetic or environmental factors.

Original languageEnglish (US)
Pages (from-to)356-361
Number of pages6
JournalJournal of AAPOS
Issue number4
StatePublished - Aug 2011

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Ophthalmology


Dive into the research topics of 'Hereditary hyperferritinemia-cataract syndrome in two large multigenerational American families'. Together they form a unique fingerprint.

Cite this