Clinical and Molecular Clues to Diagnosing Hereditary Hyperferritinemia-Cataract Syndrome: Case Report and Literature Review.

Background

Hereditary hyperferritinemia-cataract syndrome (HHCS) is a rare autosomal dominant disorder characterized by persistently elevated serum ferritin and early-onset bilateral cataracts in the absence of systemic iron overload. It is caused by pathogenic variants in the iron-responsive element (IRE) of the FTL gene, leading to dysregulated L-ferritin synthesis.

Methods

We evaluated a 12-year-old Czech girl with markedly elevated serum ferritin identified incidentally during workup for abdominal pain. Clinical assessment included biochemical, radiological, ophthalmological, and genetic testing of the proband and available family members.

Results

Magnetic resonance imaging excluded systemic iron overload, while ophthalmological evaluation revealed bilateral cataracts. Family history indicated multiple affected relatives across three generations. Genetic testing confirmed a heterozygous FTL c.-168G>C variant. Additional screening for common HFE variants revealed heterozygous H63D in several family members, with no impact on ferritin or hepcidin levels. Beyond this case, we provide a comprehensive review of HHCS, including molecular mechanisms, an updated overview of reported FTL mutations, and ophthalmological features that distinguish HHCS cataracts from other congenital cataracts.

Conclusions

This report underscores the translational relevance of combining molecular diagnostics, clinical evaluation, and family screening to improve recognition and management of HHCS, and to prevent misdiagnosis and unnecessary iron-depletion therapy.