Objective Mutations in polymerase gamma gene (POLG) are believed to be an important cause of early and juvenile onset of non-syndromic intractable epilepsy. The aim of this study is to investigate the incidence/prevalence of POLG pathogenic variants in epilespy patients of Han population through sequencing it.Methods Han Chinese patients with seizures prior valproic acid (VPA) exposure at Shanghai Children's Hospital were collected from 2015 to 2019. The clinical diagnosis was based on the 2014 Consensus Statement of Epilepsy by the International League against Epilepsy (ILAE). Blood sampling were performed before VPA treatment. The POLG gene DNA was sequenced by either the first or the next generation sequencing (NGS). The POLG variant burden was illustrated. Liver functions were tested to describe whether they experienced VPA toxicity. Results Totally 216 Han Chinese patients were included, aged from 1 month to 15 years old, 102 were male and 114 were female. The onset age was 1 month old to 13 years old, and the epilepsy course ranged from 2 weeks to about 3 years. VPA treatment was delivered for the generalized or intractable partial seizures at standard dosage. No patient experienced hepatic toxicity following VPA exposure. DNA sequencing data showed no patient had either a homozygous mutation or compound heterozygous mutation of POLG. Single heterozygous mutations of c.1150G>T and p.D384Y were found in 2 patients, and single heterozygous mutation of c.156_158dupGCA was found in 1 patient. None of these variants showed clinical significance. Conclusions Functional modifying POLG homozygous mutations and compound heterozygous mutations were not detected and VPA toxicity was not seen in the current study. POLG mutation frequency might be rare in Han Chinese, and standard VPA therapeutic dosage might be safe for Han Chinese patients.

Metachromatic leukodystrophy is an inherited lysosomal disorder caused by autosomal reces-sive mutations of ARSA gene or PASP gene,which result in the accumulation of sulfatides in the central and pe-ripheral nervous system leading to demyelination. The disease is classified into a late-infantile,juvenile and adult onset type based on the age of onset,all characterized by a variety of neurological symptoms,which eventually lead to death if untreated. There is no curative treatment for all types and stages. This review discusses pathogen-esis,clinical manifestations,diagnostic process and efficacy of current and possible future therapies such as en-zyme replacement therapy,hematopoietic stem cell transplantation and gene therapy. A longer follow up period for the above therapies are needed to come to a general conclusion and improve treatment options for metachro-matic leukodystrophy.