Parkinson’s disease (PD) is a major neurodegenerative disorder for which the etiology and pathogenesis remain as elusive as for Alzheimer's disease. PD appears to be caused by genetic and environmental factors, and pedigree and cohort studies have identified numerous susceptibility genes and loci related to PD. Autosomal recessive mutations in the genesParkin, Pink1, DJ-1, ATP13A2, PLA2G6, andFBXO7have been linked to PD susceptibility. Such mutations inATP13A2, also namedPARK9, were first identified in 2006 in a Chilean family and are associated with a juvenile-onset, levodopa-responsive type of Parkinsonism called Kufor-Rakeb syndrome (KRS). KRS involves pyramidal degeneration, supranuclear palsy, and cognitive impairment. Here we review current knowledge about theATP13A2gene, clinical characteristics of patients with PD-associatedATP13A2mutations, and models of how the ATP13A2 protein may help prevent neurodegeneration by inhibitingα-synuclein aggregation and supporting normal lysosomal and mitochondrial function. We also discuss anotherATP13A2mutation that is associated with the family of neurodegenerative disorders called neuronal ceroid lipofuscinoses (NCLs), and we propose a single pathway wherebyATP13A2mutations may contribute to NCLs and Parkinsonism. Finally, we highlight how studies of mutations in this gene may provide new insights into PD pathogenesis and identify potential therapeutic targets.

Diabetes mellitus (DM) is associated with different clinical complications. The aim of this study was to explore the prevalence of RLS in people with diabetes mellitus and compare the risk of restless leg syndrome (RLS) between diabetic and non-diabetic population. We searched for studies of RLS prevalence in DM through PubMed, Embase, and Web of Science. Two authors independently completed the literature screening, data extraction, and bias risk assessment of eligible studies. All observational studies that assessed the prevalence or risk of RLS in DM were included, where the diagnosis of RLS was based on the International Restless Legs Syndrome Study Group (IRLSSG). Percentages, odds ratio (OR) with 95% confidence intervals (CI) were used to assess pooled estimates of RLS prevalence and risk based on random-effects models. Newcastle-Ottawa-scale (NOS) or a modified NOS were used to evaluate the quality of studies. A total of 42 studies, including 835,986 participants, met the eligibility criteria for the meta-analysis. Among them, 30 studies were included in meta-analysis to analyze the prevalence of RLS. A second meta-analysis was conducted using 31 studies to determine RLS risk between diabetes and non-diabetes. The results indicate that between 25% (95% confidence interval 21%-29%) of people with diabetes showed signs of RLS, and people with diabetes had an increased risk of developing RLS compare to people without diabetes (OR 1.98, 95%CI 1.66- 2.34, p < 0.001). However, the available evidence was limited due to potential risk of bias and variability between studies (I²>75%), all of observational design. Our study suggests that the prevalence and risk of RLS might be higher in DM patients than in non-diabetes population. However, given limitations in the analysis and study design, the findings need to be corroborated in future studies. This work was supported by the Basic Conditions Platform Construction Project of Sichuan Science and Technology Department (2019JDPT0015), and the “1・3・5 project for disciplines of excellence, West China Hospital, Sichuan University” (ZYJC18003).