Novel founder intronic variant in SLC39A14 in two families causing Manganism and potential treatment strategies

Lance H. Rodan, Marissa Hauptman, Alissa M. D'Gama, Anita E. Qualls, Siqi Cao, Karin Tuschl, Fatma Al-Jasmi, Jozef Hertecant, Susan J. Hayflick, Marianne Wessling-Resnick, Edward T. Yang, Gerard T. Berry, Andrea Gropman, Alan D. Woolf, Pankaj B. Agrawal

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)


Congenital disorders of manganese metabolism are rare occurrences in children, and medical management of these disorders is complex and challenging. Homozygous exonic mutations in the manganese transporter SLC39A14 have recently been associated with a pediatric-onset neurodegenerative disorder characterized by brain manganese accumulation and clinical signs of manganese neurotoxicity, including parkinsonism-dystonia. We performed whole exome sequencing on DNA samples from two unrelated female children from the United Arab Emirates with progressive movement disorder and brain mineralization, identified a novel homozygous intronic mutation in SLC39A14 in both children, and demonstrated that the mutation leads to aberrant splicing. Both children had consistently elevated serum manganese levels and were diagnosed with SLC39A14-associated manganism. Over a four-year period, we utilized a multidisciplinary management approach for Patient 1 combining decreased manganese dietary intake and chelation with symptomatic management of dystonia. Our treatment strategy appeared to slow disease progression, but did not lead to a cure or reversal of already established deficits. Clinicians should consider testing for noncoding mutations in the diagnosis of congenital disorders of manganese metabolism and utilizing multidisciplinary approaches in the management of these disorders.

Original languageEnglish
Pages (from-to)161-167
Number of pages7
JournalMolecular Genetics and Metabolism
Issue number2
Publication statusPublished - Jun 2018


  • Congenital manganism
  • Manganese toxicity
  • SLC39A14

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology


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