title: Inherited disorders of transition metal metabolism: an update.
abstract: Elements with a biological role include six trace transition metals: manganese, iron, cobalt, copper, zinc and molybdenum. Transition metals participate in group transfer reactions such as glycosylation and phosphorylation and those that can transfer an electron by alternating between two redox states such as iron (3+/2+) and copper (2+/1+) are also very important in biological redox reactions including the reduction of molecular oxygen and the transport of oxygen. However, these trace metals are also potentially toxic, generating reactive oxygen species through Fenton chemistry. Recently, a role of trace metals in host defence ("nutritional immunity") has been recognized. The host can deprive the pathogen of a trace metal or poison it with a toxic concentration. Disorders leading to low concentrations of a trace metal can often be treated by supplementing that metal; disorders leading to excessively high concentrations can often be treated with chelating agents such as penicillamine and disodium calcium edetate. This update will address: i) the manganese/zinc transporters (because two new treatable disorders were described in 2016 - SLC39A8 deficiency and SLC39A14 deficiency); ii) copper transporter disorders because we need to improve the treatment of patients with neurological symptoms due to Wilson's disease; and iii) iron homeostasis because recent progress in research into the metabolism of iron and its regulation helps us better understand several inborn errors affecting these pathways.
authors.affiliation: Centre for Translational Omics, Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK. peter.clayton@ucl.ac.uk.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Clayton
mesh_terms: D000818:Animals; D027682:Cation Transport Proteins / Q000172:deficiency / Q000235:genetics; D002614:Chelating Agents; D003300:Copper / Q000378:metabolism; D004583:Electrons; D006031:Glycosylation; D006527:Hepatolenticular Degeneration / Q000628:therapy; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism; D008345:Manganese / Q000737:chemistry; D008661:Metabolism, Inborn Errors / Q000235:genetics*; D008670:Metals / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D009498:Neurotoxins / Q000737:chemistry; D010084:Oxidation-Reduction; D010766:Phosphorylation; D014131:Trace Elements / Q000378:metabolism*; D015032:Zinc
chemical_list: D027682:Cation Transport Proteins; D002614:Chelating Agents; D008670:Metals; D009498:Neurotoxins; C497524:SLC39A14 protein, human; C530151:SLC39A8 protein, human; D014131:Trace Elements; D008345:Manganese; D003300:Copper; D007501:Iron; D015032:Zinc