Definition Hereditary ferritinopathy (HF) or neuroferritinopathy is an autosomal-dominant, adult-onset neurodegenerative disease caused by mutations in the ferritin light chain (FTL) gene . Ferritin, the main iron-storage molecule, is a highly stable complex of 24 polypeptide subunits. Ferritin subunits show considerable amino acid sequence homology and are designated as a ferritin heavy chain (FTH1) and FTL. Thus far, all known mutations associated with HF occur in exon four of the FTL, leading to the production of an FTL polypeptide with an altered carboxyl end [2–7]. The structural defect in the ferritin molecule caused by the presence of mutant FTL polypeptides causes deregulation of cellular iron metabolism (ferritin loss of function), oxidative stress and overproduction of ferritin polypeptides (a positive feedback loop) with the formation of ferritin inclusion bodies (IBs) (a gain of toxic function) . These two mechanisms seem to be acting together to lead to the progression of the disease and neurodegeneration [8, 9]. The main neuropathological findings are the presence of intranuclear and intracytoplasmic ferritin IBs and deposition of iron in glial cells, some subsets of neurons and endothelial cells. In addition, ferritin IBs may also be found in cells of other organ systems . Initial attempts at iron chelation or depletion did not appear to be clinically effective . Clinical phenotypes The onset of clinical signs and symptoms may occur between the second and seventh decade of life with duration ranging from a few years to several decades [2–7, 11, 12]. The disease occurs equally in males and females. Hereditary ferritinopathy has been reported in Caucasian and Japanese individuals, presenting with abnormal involuntary movements. The clinical phenotype of HF may be highly variable. In fact, differences in the presentation of the disease are evident between patients with different mutations as well as among patients with the same mutation . The disease may present as a movement disorder with tremor, cerebellar signs, Parkinsonism, dystonic and choreic movement; in addition, pyramidal and pseudo-bulbar symptoms may be present. In more advanced stages, psychiatric and cognitive symptoms may become evident [2–7, 10–12].
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