Recurrent mutations in the iron regulatory element of L-ferritin in hereditary hyperferritinemia-cataract syndrome

Background and Objective. Hereditary hyperferritinemia-cataract syndrome (H HCS) is an autosomal dominant disorder characterized by bilateral cataracts and increased serum and tissue L-ferritin, in the absence of iron overload . The deregulation of ferritin production is caused by heterogeneous mutati ons in the iran regulatory element (IRE) of L-ferritin that interfere with the binding of iron regulatory proteins. Design and Methods. We have identified several patients from three unrelate d Italian families with HHCS. Iron parameters were assessed by standard met hods. The IRE element of L-ferritin was amplified by PCR using appropriate primers and directly sequenced. Results. Ferritin levels ranged from 918 mu g/L to 2490 mu g/L in the patie nts studied. In one family bilateral cataracts were diagnosed early in life , whereas in the others cataracts were diagnosed around 40-50 years. The fe male proband of family 3 presented with a severe iron deficiency anemia, wh ich was unrecognized because of the increased ferritin values. Sequencing o f the IRE element of L-ferritin in the probands of: the three families iden tified three different nucleotide substitutions (+32 G-->A, +40 A-->G and 39 C-->T) in the IRE of L-ferritin. These mutations have already been repor ted in unrelated subjects of different ethnic origins. Interpretation and Conclusions. Our findings are consistent with recurrent mutations associated with HHCS and underline the importance of this syndrom e in the differential diagnosis of unexplained hyperferritinemia. In additi on, the findings highlight the role played by transferrin saturation in the diagnosis of iron deficiency in these patients. (C) 1999, Ferrata Storti F oundation.