Hereditary hyperferritinemia-cataract syndrome (HHCS) presenting with iron deficiency anemia associated with a new mutation in the iron responsive element of the L ferritin gene in a swiss family

Hereditary hyperferritinemia-cataract syndrome (HHCS) is one of the differential diagnoses of hyperferritinemia (HF) with low or normal transferrin saturation but is usually not associated with anemia. Here, we report a case of a microcytic, hypochromic anemia with hyperferritinemia as the initial presentation of a combination of iron deficiency anemia and HHCS. The latter is an autosomal dominant disorder characterized by distinctive cataracts and HF in the absence of iron overload. Sequencing studies were carried out to look for mutations in the iron responsive element (IRE) of the L ferritin gene. A heterozygous single point mutation for a +24T to C substitution in the IRE of the L ferritin gene (= HGVS c.-176T>C) was detected which has not been described before. To evaluate the pathogenetic relevance of this new mutation, we performed family studies of parents and siblings. We could identify the father and one brother with HF, cataract, and the heterozygous +24T>C mutation. Neither the mother nor the five other siblings had HF, cataract or that mutation. We therefore conclude that this newly described heterozygous +24T>C mutation in the IRE of the L ferritin gene causes HHCS.