RÉSUMÉ
Neurodegeneration with brain iron accumulation (NBIA) encompasses a clinically and genetically heterogeneous group of rare disorders. Here, we report clinical, neuroimaging and genetic studies in twenty three Brazilian NBIA patients. In thirteen subjects, deleterious variants were detected in known NBIA-causing genes (PANK2, PLA2G6, C9ORF12, WDR45 and FA2H), including previously unreported variants in PANK2 and PLA2G6. Two patients carried rare, likely pathogenic variants in genes not previously associated with NBIA: KMT2A c.11785A > C (p.Ile3929Leu), and TIMM8A c.127T > C (p.Cys43Arg), suggesting an expansion of their associated phenotypes to include NBIA. In eight patients the etiology remains unsolved, suggesting variants undetectable by the adopted methods, or the existence of additional NBIA-causing genes.
Sujet(s)
Neuroimagerie , Humains , Brésil , Femelle , Mâle , Adulte , Adolescent , Jeune adulte , Enfant , Enfant d'âge préscolaire , Imagerie par résonance magnétique , Encéphale/imagerie diagnostique , Encéphale/métabolisme , Encéphale/anatomopathologie , Dystrophies neuroaxonales/génétique , Dystrophies neuroaxonales/imagerie diagnostique , Phosphotransferases (Alcohol Group Acceptor)/génétique , Fer/métabolisme , Troubles du métabolisme du fer/génétique , Troubles du métabolisme du fer/imagerie diagnostique , Group VI Phospholipases A2RÉSUMÉ
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.
Sujet(s)
Troubles du métabolisme du fer/imagerie diagnostique , Troubles du métabolisme du fer/génétique , Mutation , Dystrophies neuroaxonales/imagerie diagnostique , Dystrophies neuroaxonales/génétique , Neuroimagerie/méthodes , Alopécie/imagerie diagnostique , Alopécie/génétique , Troubles du rythme cardiaque/imagerie diagnostique , Troubles du rythme cardiaque/génétique , Affections des ganglions de la base/imagerie diagnostique , Affections des ganglions de la base/génétique , Céruloplasmine/déficit , Céruloplasmine/génétique , Coenzyme A ligases/génétique , Diabète/imagerie diagnostique , Diabète/génétique , Maladies neurodégénératives héréditaires/imagerie diagnostique , Maladies neurodégénératives héréditaires/génétique , Humains , Hypogonadisme/imagerie diagnostique , Hypogonadisme/génétique , Déficience intellectuelle/imagerie diagnostique , Déficience intellectuelle/génétique , Imagerie par résonance magnétique/méthodes , Protéines membranaires/génétique , Maladies neurodégénératives/imagerie diagnostique , Maladies neurodégénératives/génétique , Neurodégénérescence associée à la pantothénate kinase/imagerie diagnostique , Neurodégénérescence associée à la pantothénate kinase/génétique , Syndromes parkinsoniens/imagerie diagnostique , Syndromes parkinsoniens/génétique , Phospholipases A2/génétiqueRÉSUMÉ
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.
RESUMO A neurodegeneração com acúmulo cerebral de ferro (sigla em inglês NBIA) representa um grupo heterogêneo e complexo de doenças neurodegenerativas hereditárias, caracterizada pelo acúmulo cerebral de ferro, especialmente nos núcleos da base. O quadro clínico das NBIAs em geral inclui distúrbios do movimento, particularmente parkinsonismo e distonia, disfunção cognitiva, sinais piramidais e anormalidades da retina. As formas de NBIA descritas até o momento incluem neurodegeneração associada a pantothenase kinase (PKAN), neurodegeneração associada a phospholipase A2 (PLAN), neuroferritinopatia, aceruloplasminemia, neurodegeneração associada a beta-propeller protein (BPAN), síndrome de Kufor-Rakeb, neurodegeneração associada a mitochondrial membrane protein (MPAN), neurodegeneração associada a “fatty acid hydroxylase” (FAHN), neurodegeneração associada a coenzyme A synthase protein (CoPAN) e síndrome de Woodhouse-Sakati. Esta revisão é uma orientação para o diagnóstico das NBIAs, partindo das características clínicas e achados de neuroimagem, até a etiologia genética.