Disorders of manganese transport

Isaac Marin-Valencia, Sidney M. Gospe

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

Abstract

Manganese transport across cell membranes is highly regulated to prevent toxic accumulation or deficiency. In recent years, three autosomal recessive disorders of manganese transport have been reported. Patients with pathogenic variants in SLC30A10 manifest hypermanganesemia, dystonia, parkinsonism, liver dysfunction, and polycythemia, whereas patients with pathogenic variants in SLC39A14 have a similar neurological presentation but without polycythemia or liver disease. In both disorders, brain magnetic resonance imaging reveals T1 hyperintensities in the basal ganglia, pituitary, brainstem, and the dentate nucleus of the cerebellum. The treatment consists of chelation with disodium calcium edetate and oral iron supplementation to reduce manganese levels in blood. In contrast, patients with pathogenic variants in SLC39A8 present with infantile- or early childhood-onset manganese deficiency, together with a variety of neurodevelopmental features that include hypotonia, brain malformations, strabismus, growth retardation, and occasional seizures. Ongoing research aims to elucidate the regulatory mechanisms of manganese transport, its distribution at cellular and subcellular levels, and its role in neurotransmission, with the goal of developing new treatments.

Original languageEnglish
Title of host publicationRosenberg’s Molecular and Genetic Basis of Neurological and Psychiatric Disease
Subtitle of host publicationVolume 1
PublisherElsevier
Pages643-655
Number of pages13
ISBN (Electronic)9780128139554
DOIs
StatePublished - 1 Jan 2020
Externally publishedYes

Keywords

  • Cirrhosis
  • Congenital disorder of glycosylation
  • Manganese
  • Manganism
  • Parkinsonism
  • Polycythemia
  • Transport

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