Hereditary Disorders of Manganese Metabolism: Pathophysiology of Childhood-Onset Dystonia-Parkinsonism in Mutation Carriers and Genetic Animal Models.

Over the last decade, several clinical reports have outlined cases of childhood-onset manganese (Mn)-induced dystonia-parkinsonism, resulting from loss-of-function mutations in the Mn influx transporter gene . These clinical cases have provided a wealth of knowledge on Mn toxicity and homeostasis. However, our current understanding of the underlying neuropathophysiology is severely lacking. The recent availability of knockout (KO) murine and zebrafish animal models provide a powerful platform to investigate the neurological effects of elevated blood and brain Mn concentrations in vivo. As such, the objective of this review was to organize and summarize the current clinical literature and studies utilizing -KO animal models and assess the validity of the animal models based on the clinical presentation of the disease in human mutation carriers.