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Inherited disorders of transition metal metabolism: an update

  • SSIEM 2016
  • Published:
Journal of Inherited Metabolic Disease

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.

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Acknowledgements

I would like to particularly thank the following colleagues for their collaboration on investigation of disorders of manganese homeostasis: Karin Tuschl, Philippa Mills, Steve Wilson, Manju Kurian, Esther Meyer, Kling Chong and the others authors of the Tuschl et al papers.

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Authors and Affiliations

  1. Centre for Translational Omics, Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK

    Peter T. Clayton

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  1. Peter T. Clayton
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Correspondence to Peter T. Clayton.

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All studies in the author’s centre were conducted with ethical approval and signed consent from subjects/parents.

No identifying information about patients is included in the article.

All institutional and national guidelines for the care and use of laboratory animals were followed.

Conflict of interest

Peter Clayton declares he has no conflict of interest with regard to information presented in this review. He does receive consultation fees from Actelion.

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Communicated by: John H. Walter

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Clayton, P.T. Inherited disorders of transition metal metabolism: an update. J Inherit Metab Dis 40, 519–529 (2017). https://doi.org/10.1007/s10545-017-0030-x

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