Mutation in the gene encoding ferritin light polypeptide causes dominant adult-onset basal ganglia disease

We describe here a previously unknown, dominantly inherited, late-onset bas al ganglia disease, variably presenting with extrapyramidal features simila r to those of Huntington's disease (HD) or parkinsonism. We mapped the diso rder, by linkage analysis, to 19q13.3, which contains the gene for ferritin light polypeptide (FTL). We found an adenine insertion at position 460-461 that is predicted to alter carboxy-terminal residues of the gene product. Brain histochemistry disclosed abnormal aggregates of ferritin and iron. Lo w serum ferritin levels also characterized patients. Ferritin, the main iro n storage protein, is composed of 24 subunits of two types (heavy, H and li ght, L) which form a soluble, hollow sphere(1). Brain iron deposition incre ases normally with age, especially in the basal ganglia, and is a suspected causative factor in several neurodegenerative diseases(2) in which it corr elates with visible pathology(3), possibly by its involvement in toxic free -radical reactions(4). We found the same mutation in five apparently unrela ted subjects with similar extrapyramidal symptoms. An abnormality in ferrit in strongly indicates a primary function for iron in the pathogenesis of th is new disease, for which we propose the name 'neuroferritinopathy'.