Manganese transport disorder: novel SLC30A10 mutations and early phenotypes

Mov Disord. 2015 Jun;30(7):996-1001. doi: 10.1002/mds.26202. Epub 2015 Mar 17.

Abstract

Background: SLC30A10 mutations cause an autosomal recessive disorder, characterized by hypermanganesaemia, polycythemia, early-onset dystonia, paraparesis, or late-onset parkinsonism, and chronic liver disease. This is the first identified inborn error of Mn metabolism in humans, reported in 10 families thus far.

Methods: Methods for this study consisted of clinical examination, neuroimaging studies (MRI), serum dosages, and SLC30A10 genetic analysis.

Results: We describe early disease manifestations (including videos) in 5 previously unreported Indian children, carrying novel homozygous SLC30A10 mutations. Gait and speech disturbances, falls, dystonias, and central hypotonia were the presenting neurological features, starting within the first 5 years of life. All children also had severe hypermanganesemia, polycythemia, variable degree of liver disease, and marked brain MRI T1 hyperintensities.

Conclusions: Our findings expand the mutational and clinical spectra of this recently recognized disorder. An early diagnosis is warranted, because treatment with manganese-chelating agents, iron supplementation, or their combination might improve symptoms and prevent progression of this otherwise potentially fatal disease. © 2015 International Parkinson and Movement Disorder Society.

Keywords: SLC30A10; dystonia; genetics; manganese; metabolic inherited disease.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Cation Transport Proteins / genetics*
  • Child, Preschool
  • Consanguinity
  • Dystonia / blood
  • Dystonia / etiology
  • Dystonia / genetics*
  • Dystonia / physiopathology*
  • Female
  • Humans
  • Male
  • Manganese / metabolism*
  • Metal Metabolism, Inborn Errors / blood
  • Metal Metabolism, Inborn Errors / complications
  • Metal Metabolism, Inborn Errors / genetics*
  • Metal Metabolism, Inborn Errors / physiopathology*
  • Mutation
  • Pedigree
  • Phenotype
  • Zinc Transporter 8

Substances

  • Cation Transport Proteins
  • SLC30A8 protein, human
  • Zinc Transporter 8
  • Manganese