FTL +32G>C Mutation in Hereditary Hyperferritinemia Cataract Syndrome: a New Italian Family

Abstract

Background: We described a new Italian family with seven members affected by hereditary hyperferritinaemia cataract syndrome (HHCS). It is a rare autosomal dominant disease caused by mutations of the iron-responsive element (IRE) of the ferritin light chain gene (FTL). These mutations inhibit the interaction between IRE and the iron responsive protein (IRP), with concomitant upregulation of FTL synthesis. Methods: The family diagnoses of HHCS took place after finding high ferritin levels in a six-year-old girl. The family history revealed the presence of early-onset cataracts and hyperferritinaemia (1129 ng/mL) in her 34 year old mother, were performed, for all subjects, clinical, haematological, biochemical and genetic analysis. Ophthalmological examinations were performed at the time of diagnosis and again after three years for follow up. Results: Seven members of the family had bilateral and symmetrical cataracts, normal iron and haematological parameters except for high serum ferritin levels. Genetic testing confirmed the diagnosis of HHCS, demonstrating the presence of a heterozygous point mutation at position +32 (c.-168G>C) in the FTL gene. Conclusion: The ophthalmological follow-up showed slowly progressive cataracts mainly involving the nucleus, with characteristics of lens opacity and visual acuity data underlining a benign feature of syndrome. This case shows how important the family history is in reaching a correct diagnosis and avoiding unnecessary and invasive analysis, such as liver biopsy, the consequences of unwarranted treatment such as chelation therapy and adverse effects of phlebotomy. HHCS should be considered in the differential diagnosis of childhood hyperferritinaemia, especially in the presence of normal transferrin saturation.