Pathophysiology and Treatment of Neurodegeneration with Brain Iron Accumulation in the Pediatric Population

摘要

Opinion statement: Syndromes of neurodegeneration with brain iron accumulation (NBIA) are characterized by increased iron deposition in the basal ganglia leading to complex progressive neurological symptoms. Several genetically distinct subforms have been recognized. In addition to pantothenate kinase-associated neurodegeneration (PKAN, NBIA1) and PLA2G6-associated neurodegeneration (PLAN, NBIA2), further genetic causes continue to be identified. Most of these present in childhood and are inherited following an autosomal recessive trait. However, the clinical and pathological spectrum has broadened and new age-dependent presentations have been described and there is overlap between the different NBIA disorders and with other diseases (such as spastic paraplegias, leukodystrophies and neuronal ceroid lipofuscinosis). Thus, additional clinical information (e.g., radiological findings such as precise patters of deposition of iron or co-occurrence of white matter lesions) may be useful when prioritizing genetic screening. Neuropathological work-up demonstrated variable involvement of iron deposition, but also Lewy bodies, neurofibrillary tangles and spheroid bodies. Treatment remains symptomatic. Here we review characteristic features of NBIA syndromes with a focus on pediatric cases.