Neurodegeneration with brain iron accumulation (NBIA) is an umbrella term encompassing various inherited neurological disorders characterised by abnormal iron accumulation in basal ganglia. We aimed to study the clinical, radiological and molecular spectrum of disorders with NBIA. All molecular-proven cases of NBIA presented in the last 5 years at 2 tertiary care genetic centres were compiled. Demographic details and clinical and neuroimaging findings were collated. We describe 27 individuals from 20 unrelated Indian families with causative variants in 5 NBIA-associated genes. PLA2G6-associated neurodegeneration (PLAN) was the most common, observed in 13 individuals from 9 families. They mainly presented in infancy with neuroregression and hypotonia. A recurrent pathogenic variant in COASY was observed in two neonates with prenatal-onset severe neurodegeneration. Pathogenic bi-allelic variants in PANK2, FA2H and C19ORF12 genes were observed in the rest, and these individuals presented in late childhood and adolescence with gait abnormalities and extrapyramidal symptoms. No intrafamilial and interfamilial variability were observed. Iron deposition on neuroimaging was seen in only 6/17 (35.3%) patients. A total of 22 causative variants across 5 genes were detected including a multiexonic duplication in PLA2G6. The variants c.1799G > A and c.2370 T > G in PLA2G6 were observed in three unrelated families. In silico assessments of 8 amongst 9 novel variants were also performed. We present a comprehensive compilation of the phenotypic and genotypic spectrum of various subtypes of NBIA from the Indian subcontinent. Clinical presentation of NBIAs is varied and not restricted to extrapyramidal symptoms or iron accumulation on neuroimaging.

神经变性伴脑铁积聚 (NBIA) 是一个总称，包括各种以基底节铁异常积聚为特征的遗传性神经系统疾病。我们旨在研究 NBIA 疾病的临床、放射学和分子谱。汇总了过去 5 年在 2 个三级医疗遗传中心呈现的所有经分子学证实的 NBIA 病例。整理了人口统计学详细信息以及临床和神经影像学发现。我们描述了来自 20 个无关的印度家庭的 27 个人，他们在 5 个 NBIA 相关基因中具有致病变异。PLA2G6 相关神经变性 (PLAN) 是最常见的，在来自 9 个家庭的 13 个个体中观察到。他们主要在婴儿期出现神经退化和肌张力减退。在两名产前发病的严重神经变性新生儿中观察到 COASY 中的复发性致病性变异。在其余人中观察到 PANK2、FA2H 和 C19ORF12 基因的致病性双等位基因变异，这些个体在儿童晚期和青春期出现步态异常和锥体外系症状。没有观察到家庭内和家庭间的变异性。仅 6/17 (35.3%) 患者在神经影像学上发现铁沉积。共检测到 5 个基因的 22 个致病变异，包括 PLA2G6 中的多外显子重复。在三个不相关的家族中观察到 PLA2G6 中的变体 c.1799G > A 和 c.2370 T > G。还对 9 个新变体中的 8 个进行了计算机评估。我们提供了印度次大陆 NBIA 各种亚型的表型和基因型谱的综合汇编。NBIA 的临床表现多种多样，并不局限于锥体外系症状或神经影像学上的铁积聚。