UCL Great Ormond Street Institute of Child Health


Great Ormond Street Institute of Child Health


Dr Karin Tuschl

Inherited Manganese Transporter Defects

Manganese is an essential trace metal and critical for brain physiology and development. However, excess manganese is neurotoxic and leads to dystonia-parkinsonism, psychiatric and intellectual disability.

Our research has identified two manganese transporter defects associated with manganese neurotoxicity – hypermanganesaemia with dystonia 1 (HMNDYT1) and 2 (HMNDYT2). They are caused by loss-of-function mutations in SLC30A10 and SLC39A14, respectively, that encode manganese transporters that act in conjunction to mediate metal excretion. Manganese deposition in the brain leads to progressive, childhood-onset dystonia-parkinsonism associated with significant disability and premature death.

Our lab is part of Zebrafish research at UCL. We use manganese transporter mutant zebrafish as models for manganese overload/deficiency in order to dissect how metal dyshomeostasis disrupts neurons, synapses and circuit function with the view to identifying new therapeutic targets. In addition, we are working to develop a novel, orally bioavailable Mn chelator to improve treatment for disorders associated with Mn neurotoxicity.