A diagnostic approach for neurodegeneration with brain iron accumulation: clinical features, genetics and brain imaging

Abstract

Neurodegeneration with brain iron accumulation (NBIA) represents a heterogeneous and complex group of inherited neurodegenerative diseases, characterized by excessive iron accumulation, particularly in the basal ganglia. Common clinical features of NBIA include movement disorders, particularly parkinsonism and dystonia, cognitive dysfunction, pyramidal signs, and retinal abnormalities. The forms of NBIA described to date include pantothenase kinase-associated neurodegeneration (PKAN), phospholipase A2 associated neurodegeneration (PLAN), neuroferritinopathy, aceruloplasminemia, beta-propeller protein-associated neurodegeneration (BPAN), Kufor-Rakeb syndrome, mitochondrial membrane protein-associated neurodegeneration (MPAN), fatty acid hydroxylase-associated neurodegeneration (FAHN), coenzyme A synthase protein-associated neurodegeneration (CoPAN) and Woodhouse-Sakati syndrome. This review is a diagnostic approach for NBIA cases, from clinical features and brain imaging findings to the genetic etiology.

Woodhouse-Sakati Syndrome With Psychosis and Basal Ganglia Calcification: A Case Report

“…It is considered one of the neurodegeneration with brain iron accumulation disorders [4]. Our patient presented with classical features of the disease including neurological, endocrinal, and ectodermal symptoms [3].…”

Hepcidin and its therapeutic potential in neurodegenerative disorders

“…NBIA is a heterogeneous and complex group of inherited neurodegenerative diseases with pathological features of iron overload in the globus pallidus and other brain regions . Clinical features include parkinsonism and severe dystonia, gait abnormalities, cognitive disorders, pyramidal signs, and retinal abnormalities . So far, mutations in 10 genes have been identified including ferritin light chain (FTL) and ceruloplasmin (CP).…”

“…Clinical features include parkinsonism and severe dystonia, gait abnormalities, cognitive disorders, pyramidal signs, and retinal abnormalities . So far, mutations in 10 genes have been identified including ferritin light chain (FTL) and ceruloplasmin (CP). Abnormalities in iron metabolism, mainly in neurons or astrocytes, have been demonstrated as a direct cause for neuroferritinopathy (NFP) and aceruloplasminaemia (CPM), which are induced by a mutation in FTL and CP, respectively .…”

“…The connection between the mutations in other genes of NBIA, including PLA2G6 (PLAN), WDR45 (BPAN), ATP13A2 (PARK9) (Kufor‐Rakeb syndrome), C19orf12 (MPAN), FA2H (FAHN), CoASY (CoPAN), and C2orf37 (Woodhouse‐Sakati syndrome) and brain iron metabolism is currently unknown. However, these genes are known to be mainly involved in lipid metabolism (PLA2G6, FA2H, CoASY, and potentially C19orf12) and autophagy (WDR45 and ATP13A2), while recent evidence has shown that autophagy is crucially involved in cellular iron handling and that a number of genes involved in lipid and amino acid metabolism are required for the iron‐dependent cell death, ferroptosis . These findings suggest that autophagy and lipid metabolism both may be associated with iron metabolism.…”

Neurodegeneration with brain iron accumulation

“…In view of the complexities of the various clinical syndromes and patent overlapping between then, to reach a specific diagnosis is particularly challenging. In the article by Salomão et al 8 , in this issue, the authors provide a comprehensive review of the NBIA spectrum along with detailed clinical and radiological features that help to distinguish among the various types. Genetic tests, when available, should aid in the diagnosis.…”