ABSTRACT
Neurodegeneration with brain iron accumulation (NBIA) is a complex group of hereditary progressive neurodegenerative diseases characterized by deposition of iron in the basal ganglia. Twelve genetic forms of this disorder have been identified in previous studies. Though they have different inheritance mechanisms all are usually associated with abnormal brain MRI findings. One of NBIA types is an X-linked disorder known as Beta-propeller Protein Associated Neurodegeneration (BPAN). Herein we describe the case of a 4-year-old girl with 2 episodes of febrile seizures, a brain MRI showing nonspecific hyperintense signal in the dentate nucleus area, and delays in language and communication development. Her diagnosis was made based on a genetic evaluation where exome sequencing revealed a mutation in the position chrX:48.933.022 region of the WDR45 gene. The literature describes different clinical presentations for BPAN, each with a different prognosis, suggesting a wide range of possible symptoms of BPAN, including mild cognitive delay and even epileptic encephalopathy (EE). (AU)
Subject(s)
Humans , Female , Child, Preschool , Neuroaxonal Dystrophies/diagnosis , Iron Metabolism Disorders/diagnosis , Seizures, Febrile , Language Development Disorders , Carrier Proteins/genetics , Neuroaxonal Dystrophies/genetics , Iron Metabolism Disorders/geneticsABSTRACT
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.