Discovering strange diseases: NBIA

J Neural Transm. 2013 Apr;120(4):695-703. doi: 10.1007/s00702-012-0922-8. Epub 2012 Dec 2.

Excess iron harms the brain: the syndromes of neurodegeneration with brain iron accumulation (NBIA).

Schneider SA, Bhatia KP.

Source

Department of Neurology, University Kiel, Arnold Heller Str. 3, 24105, Kiel, Germany. s.schneider@neurologie.uni-kiel.de

Abstract

Regulation of iron metabolism is crucial: both iron deficiency and iron overload can cause disease. In recent years, our understanding of the syndromes of Neurodegeneration with Brain Iron Accumulation (NBIA) continues to grow considerably. These are characterized by excessive iron deposition in the brain, mainly the basal ganglia. Pantothenate kinase-associated neurodegeneration (PKAN, NBIA1) and PLA2G6-associated neurodegeneration (PLAN, NBIA2) are the core syndromes, but several other genetic causes have been identified (including FA2H, C19orf12, ATP13A2, CP and FTL). These conditions show a wide clinical and pathological spectrum, with clinical overlap between the different NBIA disorders and other diseases including spastic paraplegias, leukodystrophies, and neuronal ceroid lipofuscinosis. Lewy body pathology was confirmed in some clinical subtypes (C19orf12-associated neurodegeneration and PLAN). Research aims at disentangling the various NBIA genes and their related pathways to move towards pathogenesis-targeted therapies. Until then treatment remains symptomatic. Here we will introduce the group of NBIA syndromes and review the main clinical features and investigational findings.