• hyperferritinaemia
• iron metabolism
• iron responsive element
• neurodegenerative disorders
• neuroferritinopathy

• HHCS, hyperferritinaemia cataract syndrome
• IRE, iron responsive element
• IRP, iron regulatory protein

Ferritin consists of two subunit types, H and L, which assemble in different proportions in a 24-mer protein.¹ The H-subunit has ferroxidase activity and is mainly found in cell cytoplasm, where it has the major function of sequestering and detoxifying unwanted iron. The L-subunit has no catalytic activity on its own, but assists the functionality of the H-subunit² and is also found in minor amounts in serum.³ Two types of genetic disorder are associated with mutations of the L-ferritin gene (FTL), both with autosomal dominant transmission. The first, hereditary hyperferritinaemia cataract syndrome (HHCS), is caused by mutations in the regulatory iron responsive element (IRE) in the 5′UTR of the transcript that reduce binding affinity to the iron regulatory proteins (IRPs) and lead to constitutive upregulation of the protein in tissue and serum.^4–8 Subjects with the mutations show high levels of serum ferritin (500–2000 μg/l) and often early-onset bilateral cataracts⁶ likely caused by protein aggregation in the lens,⁹ but do not present alterations in iron metabolism. The disorder has been extensively studied and more than 21 different causative mutations have been identified.^9,10 The second type of genetic disorder, neuroferritinopathy, is rare and few families have been identified. It is associated with an adenine insertion at position 460–461 in the coding region (exon 4) of the gene that causes a frame shift alteration of the C-terminus of the L-ferritin polypeptide.¹¹ Affected subjects show late-onset movement disorders, iron deposition in the brain basal ganglia, and low serum ferritin levels.^12,13 It is unclear whether the iron deposition in the brain is caused by a quantitative defect of L-ferritin or by an abnormal functionality caused by …