Clinical features of ferritinopathy

Abstract

Iron is a bioactive metal essential for normal cellular functions. However, excessive iron leads to cell death because iron enhances oxidative stress due to the generation of highly cytotoxic hydroxyl radicals. Therefore, complicated cellular pathways have been developed to allow for the transport, trafficking and compartmentalization of iron in cells. The tissue iron content is critically regulated by several iron metabolic molecules.

Neurodegeneration with brain iron accumulation (NBIA) comprises a heterogeneous group of inherited neurodegenerative disorders collectively characterized by extrapyramidal movement disorders and abnormal iron accumulation in the deep basal ganglia nuclei of the brain. Ferritinopathy is one of NBIA and a progressive adult–onset movement disorder caused by mutations in the ferritin light chain gene. The major clinical symptoms are focal onset chorea or focal dystonia. It is characterized by iron and ferritin aggregate accumulation in brain and visceral organs, low serum ferritin levels, and brain MR images of T2 * signal loss in the dentate nuclei, thalami and globus pallidus. In advanced cases, the basal ganglia showed internal cystic degeneration. To date, nine causative mutations have been identified and eight of them are frame–shift mutations in the exon 4 of L–ferritin gene.