Neuroferritinopathy in a Japanese Family With a Duplication in the Ferritin Light Chain Gene

Neuroferritinopathy is a rare autosomal dominant movement disorder with the deposition of iron and ferritin within the basal ganglia. Four different pathogenic mutations in the ferritin light polypeptide (FTL) gene have been reported.1–4 The variety of its clinical features makes the diagnosis of neuroferritinopathy difficult. In this study we investigated a Japanese family with neuroferritinopathy to clarify the phenotypic and genetic spectrum of neuroferritinopathy. ### Proband. A 42-year-old Japanese man first developed hand tremors in his middle teens. He noticed his right foot dragging at age 35, and generalized hypotonia, hyperextensibility, aphonia, micrographia, hyperreflexia, and cognitive impairment (IQ = 66) at age 42. His unsteady gait with long steps, with his arms and legs dangling, seemed to be due mainly to hypotonus. Rigidity, spasticity, dystonia, or chorea were not observed. His serum ferritin concentration was 5 μg/L (normal = 33 to 330). A brain MRI revealed bilateral symmetric cystic changes of the pallidum and the striatum. Hyperintense lesions in the T2-weighted imaging involved the thalamus, dentate nucleus, and substantia nigra. The proband's mother had developed hand tremors at age 10. She presented with difficulty walking at age 35 and developed …