Department of Pediatrics, Peking University First Hospital, Beijing.
Eur J Neurol. 2013 Feb;20(2):322-30. doi: 10.1111/j.1468-1331.2012.03856.x. Epub 2012 Aug 31.
To perform a follow-up of 25 Chinese children with gene-confirmed PLA2G6-associated neurodegeneration (PLAN).
We recruited patients with infantile neuroaxonal dystrophy (INAD) according to the criteria proposed by Nardocci et al. Follow-up was conducted from 7 months to 8 years after the first visit. The PLA2G6 gene was sequenced, and copy number variation (CNV) was detected in patients with only one mutant allele and in mutation-negative patients. Patients with late-onset PLAN until 2012 were reviewed.
All patients with INAD exhibited rapid decline in motor and mental function, consistent with previous reports from other populations. Epileptic seizures occurred in 16.7%. One teenager with late-onset PLAN was diagnosed and followed up. The age of disease onset in published late-onset PLAN ranged between 18 months and 37 years. Initial presentations included gait instability (79.0%), mood/behavior changes (10.5%), dysarthria (5.26%) and cognitive deterioration (5.3%). Compared with INAD, cerebellar atrophy (42.1%) was less frequent in the late-onset cases, with cerebral atrophy more common (71.4%). Brain iron accumulation was seen in 52.6%. PLA2G6 mutations were identified by DNA sequencing in 92.3% of clinically diagnosed INAD cases and in the late-onset case. Twenty-seven different mutations were found, of which 13 were novel. No CNVs were detected. Maternal uniparental disomy was confirmed in one INAD case.
This is the largest report on PLAN in the Chinese population. We suggest that PLA2G6 should be screened in any patient exhibiting progressive gait disturbance, bradykinesia, dysarthria, tremors, mood/behavior changes or cognitive decline, especially when associated with cerebellar atrophy and/or iron accumulation and/or cerebral atrophy.
对 25 例基因确诊的 PLA2G6 相关神经退行性疾病（PLAN）患儿进行随访。
根据 Nardocci 等人提出的标准，我们招募了婴儿神经轴突营养不良（INAD）患者。从首次就诊后 7 个月到 8 年进行随访。对仅一个突变等位基因的患者和突变阴性患者进行 PLA2G6 基因测序和拷贝数变异（CNV）检测。回顾 2012 年前发病的迟发性 PLAN 患者。
所有 INAD 患者均表现为运动和精神功能迅速下降，与其他人群的既往报道一致。癫痫发作发生率为 16.7%。1 例迟发性 PLAN 青少年患者被诊断并随访。已发表的迟发性 PLAN 发病年龄在 18 个月至 37 岁之间。首发表现包括步态不稳（79.0%）、情绪/行为改变（10.5%）、构音障碍（5.26%）和认知恶化（5.3%）。与 INAD 相比，迟发性病例小脑萎缩（42.1%）较少见，脑萎缩更常见（71.4%）。52.6%有脑铁沉积。92.3%的临床诊断 INAD 病例和迟发性病例通过 DNA 测序发现 PLA2G6 突变，共发现 27 种不同突变，其中 13 种为新突变。未检测到 CNV。在 1 例 INAD 病例中证实存在母源单亲二体性。
这是中国人群中关于 PLAN 的最大报告。我们建议在任何出现进行性步态障碍、运动迟缓、构音障碍、震颤、情绪/行为改变或认知下降的患者中，特别是当伴有小脑萎缩和/或铁沉积和/或脑萎缩时，应筛查 PLA2G6。
