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Hypermanganesemia with dystonia type 2 is a rare autosomal recessive neurodegenerative disorder caused by biallelic loss-of-function variants in SLC39A14. Patients present with progressive dystonia, parkinsonian features, elevated serum manganese, and characteristic bilateral basal ganglia MRI signal changes in T1 and T2/FLAIR sequences. Three unrelated pediatric patients were genetically confirmed to harbor SLC39A14 mutations, each with hypermanganesemia and dystonia consistent with MONDO:0014864 ([PMID:36138644]). No familial segregation data were reported.
Chelation therapy with calcium disodium edetate led to clinical improvement in two of the three treated patients, demonstrating that early intervention can alter disease trajectory. These findings underscore the importance of prompt molecular diagnosis and treatment initiation in improving motor and cognitive outcomes in this treatable disorder. Key Take-home: Genetic confirmation of SLC39A14 deficiency enables targeted chelation therapy to mitigate progression of hypermanganesemia with dystonia type 2.
Gene–Disease AssociationLimitedThree unrelated probands with confirmed biallelic SLC39A14 variants; no segregation or mechanistic studies Genetic EvidenceLimitedEvidence from 3 unrelated cases with biallelic SLC39A14 variants reaches limited genetic evidence level Functional EvidenceNo evidenceNo experimental functional studies specific to SLC39A14 variants in hypermanganesemia with dystonia type 2 |