Hereditary Hyperferritinemia Caratact Syndrom due to a point mutation at position 32 in the IRE (iron responsive element) of the ferritin light chain – the first family in Germany

Aims: High serum ferritin levels are highly suggestive for iron overload or systemic inflammation. However, high ferritin levels may also be due to the hereditary hyperferritinemia cataract syndrome (HHCS), a rare condition with elevated ferritin light chain production and premature cataract. It is caused by mutations within the iron responsive element (IRE) of the L-ferritin mRNA (FTL gene, MIM# 134790) which disrupts binding of the iron-regulatory proteins (IRP1 and 2) resulting in an uncontrolled translation of L-ferritin translation and its deposition within the crystalline lens causing cataract. Thus far, HHCS has been identified in Great Britain, Italy, France and India, but not in Germany.

Results: We here describe the clinical and molecular characterization of the first index family in Germany. We identified a family with a two generation history of premature cataract in otherwise healthy individuals and elevated ferritin levels (between 3 and 5-fold upper normal limit) but no apparent iron overload. The father and all 3 children aged 18 to 24 years at the time of diagnosis were affected, but with variable involvement of the lens. While the father and the youngest daughter had undergone cataract surgery very early on (20 and 14 years of age), the two sons were less severely affected and lens replacement was so far not needed. Sequence analysis of the FTL gene showed a point mutation at position 32 with G>A change in all involved family members which is known to prevent binding of IRP1 to IRE.

Conclusion: HHCS is an important differenzial diagnosis in patients with high ferritin levels. Importantly, patients with HHCS can be spared from invasive diagnosis such as liver biopsy.