Neurodegeneration with brain iron accumulation.
OBJECTIVE
Recent years have witnessed the discoveries of several genes causing neurodegeneration with brain iron accumulation (NBIA) and subsequently their novel classification scheme was suggested. The first results of treatments with modern chelating drugs are also being published.


RESULTS
Most recently, mutations in the c19orf12 gene encoding a mitochondrial protein of unknown function were identified in patients suffering from hitherto unknown NBIA presenting with a clinical phenotype similar to pantothenate kinase-associated neurodegeneration (PKAN) but with a slightly later onset. A case study has shown that mutations in the fatty-acid 2-hydroxylase gene may lead to various phenotypes combining the features of leukodystrophy and NBIA, supporting that abnormal metabolism of myelin and iron accumulation may have a common cause. A phase-II pilot study did not find any clinical improvement after chelating treatment in a group of PKAN patients. However, benefits of chelating treatment have been observed in individual patients with PKAN and idiopathic NBIA in another study.


CONCLUSIONS
This review gives an outline of the clinical presentations of recently discovered NBIA syndromes and summarizes the clues to their differential diagnosis. While chelating treatment still remains experimental, advances have been made regarding the indications of deep brain stimulation in symptomatic treatment of NBIAs manifesting with generalized dystonia.
Department of Neurology, Center of Clinical Neuroscience, 1st Faculty of Medicine, General University Hospital in Prague, Charles University in Prague, Prague, Czech Republic. pdusek@gmail.com
Petr
P
Dusek
Susanne A
SA
Schneider
D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003937:Diagnosis, Differential; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000627:therapeutic use; D024101:Mitochondrial Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000473:pathology*
C568481:C19orf12 protein, human; D007502:Iron Chelating Agents; D024101:Mitochondrial Proteins; D007501:Iron