[Clinical features of neuroferritinopathy]

Neuroferritinopathy is an autosomal dominant basal ganglia disease with iron accumulation caused by a mutation of the gene encoding ferritin light polypeptide (FTL). Six pathogenic mutations in the FTL gene have so far been reported. One such mutation was found in a Japanese family, thus suggesting that a new mutation in the FTL gene can therefore occur anywhere in the world. The typical clinical features of neuroferritinopathy are dystonia (especially orofacial dystonia related to speech and leading to dysarthrophonia) and involuntary movement, but such features vary greatly among the affected individuals. The findings of excess iron storage and cystic changes involving the globus pallidus and the putamen on brain MRI. and low serum ferritin levels are characteristic in neuroferritinopathy. Brain histochemistry shows abnormal aggregates of ferritin and iron throughout the central nervous system. Iron atoms are stored in the central cavity of the ferritin polymer and the E-helices of ferritin play an important role in maintaining the central cavity. A mutation in exon 4 of the FTL gene is known to alter the structure of E-helices, thereby leading to the release of free iron and excessive oxidative stress. Iron depletion therapy by iron chelation in symptomatic patients has not been shown to be beneficial, however before the nset of clinical symptoms, such a treatment strategy may still have some benefit. Neuroferritinopathy should therefore be considered in all patients presenting with basal ganglia disorders of unknown origin. These characteristic MRI findings may help to differentiate neuroferritinopathy from other diseases showing similar clinical features.