Abstrakt
Iron is an essential element necessary for energy production, DNA and neurotransmitter synthesis, myelination and phospholipid metabolism. Neurodegeneration with brain iron accumulation (NBIA) involves several genetic disorders, two of which, aceruloplasminemia and neuroferritinopathy, are caused by mutations in genes directly involved in iron metabolic pathway, and others, such as pantothenate-kinase 2, phospholipase-A2 and fatty acid 2-hydroxylase associated neurodegeneration, are caused by mutations in genes coding for proteins involved in phospholipid metabolism.
Phospholipids are major constituents of myelin and iron accumulation has been linked to myelin derangements. Another group of NBIAs is caused by mutations in lysosomal enzymes or transporters such as ATP13A2, mucolipin-1 and possibly beta-galactosidase and alpha-fucosidase.
Increased cellular iron uptake in these diseases may be caused by impaired recycling of iron which normally involves lysosomes. Abnormal iron utilization by mitochondria, as has been proposed in Friedreich's ataxia, is another possible mechanism of iron accumulation.
Other, more common degenerative movement disorders, such as Parkinson's disease, Huntington's disease, multiple system atrophy and progressive supranuclear palsy also exhibit increased brain iron content Finally, brain iron deficiency has been implicated in restless legs syndrome. This review provides an update on recent findings related to genetics, pathogenic mechanisms, diagnosis, and treatment of movement disorders associated with dysregulation of brain iron.
We also propose a new classification of NBIAs.