To investigate the effects of chelation therapies in hypermanganesemia secondary to a SLC39A14 mutation.

Inherited Hypermanganesemia is a rare condition caused by mutations in either the SLC39A14 or SLC30A10 gene. The disease typically manifests between 6 months and 3 years of age characterized by rapidly progressive parkinsonism-dystonia due to neurodegeneration.

A 9-month old male with a family history of hypermanganesemia presented with truncal ataxia, dystonic neck movements, bulbar dysfunction, and bilateral cortical thumbs. Cognitive exam revealed no abnormalities. Brain MRI showed T1 hyperintensity throughout the basal ganglia, while blood manganese was elevated at 106.9 ug/L (4.2 - 16.5 ug/L). Whole genome sequencing found a homozygous mutation in SLC39A14 at c.382C>T (p.R128W), confirming the diagnosis of inherited hypermanganesemia.

First agent of chelation therapy was started 15 days after the onset of symptoms with 500 mg Na2CaEDTA once daily for 5 consecutive days every 30 days. After two infusion cycles, the frequency was increased to 500 mg once daily for 3 consecutive days every week. The lowest blood Mn level recorded was 86.4 ug/L. Na2CaEDTA infusions were stopped after 10 months due to worsening clinical symptoms and burden of treatment. Second agent of chelation therapy with oral administration of 2,3 dimercaptosuccinic acid (DMSA) was given afterwards 3 days on and 11 days off, but also failed to bring blood level of Mn down. Treatment with DMSA was discontinued after 6 months of treatment due to poor tolerability and lack of benefit. He continued to show progression in his symptoms resulting in severe dystonia and loss of voluntary movements.

Patients with inherited hypermanganesemia could benefit from early detection and treatment with chelation therapy. However, our patient did not respond to chelation therapy despite beginning treatment within 15 days of initial symptom onset.