[Clinical feature of neuroferritinopathy]

Neuroferritinopathy is an autosomal dominant, adult-onset disorder characterized by the deposition of iron and ferritin in the brain and a decreased level of serum ferritin. The disease is caused by mutations of the gene encoding ferritin light chain polypeptide. Seven pathogenic mutations have so far been reported, and two of the mutations were found in Japanese families. The mutations are predicted to affect tertiary structure and stability of the ferritin light chain polypeptide and may cause inappropriate iron release from feritin polymers. The excess iron may cause oxidative stress and lead to cell and tissue damage. The typical clinical features are dystonia and involuntary movement. Some patients may present cerebellar ataxia and cognitive decline. The clinical features appear to be restricted to the nervous system. The variety of MRI findings including T(2) hypointense lesions reflecting iron deposits, cystic degeneration of the basal ganglia, and cortical atrophy are characteristic of neuroferritinopathy. Iron depletion therapy by iron chelation in symptomatic patients has not been shown to be beneficial. Recent study shows the iron deposition in neuroferritinopathy begins in early childhood before symptomatic presentation. This finding suggests the importance of early intervention of therapy.