Background: To perform a follow-up of 25 Chinese children with gene-confirmed PLA2G6-associated neurodegeneration (PLAN). Methods: 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. Results: 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. Conclusions: 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.
[1]Peking Univ, Hosp 1, Dept Pediat, Beijing 100034, Peoples R China.
[2]Fudan Univ, Sch Life Sci, Shanghai 200433, Peoples R China.
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