Hereditary Hyperferritinemia-cataract Syndrome

Abstract

Hereditary hyperferritinemia-cataract syndrome (HHCS) is a rare autosomal dominant disorder associated with high plasma ferritin concentration without iron overload and early-onset bilateral cataract. The deregulation of ferritin production in HHCS is caused by mutations in the iron-responsive elements (IREs) of the ferritin L-subunit gene (FTL gene) – interfering with the high-affinity interaction between IREs and iron regulatory proteins (IRPs), disturbing the negative regulatory control of ferritin synthesis and resulting in excessive production of L-ferritin. We report a 44-year-old woman initially suspected of having hereditary haemochromatosis and later together with family members diagnosed with HHCS. Genetic analysis showed heterozygosity for a G32T point mutation (Paris 2 mutation) in the IRE located in the 5′ untranslated region (UTR) of the FTL gene. The differential diagnosis of hereditary haemochromatosis and HHCS together with the rarity and the versatile phenotype in HHCS obscures the diagnostic process, which emphasises the importance of the correct diagnosis of HHCS in order to prevent unnecessary phlebotomy.