Hypermanganesemia with Dystonia 1

In: GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993.
[updated ].


Clinical characteristics: Hypermanganesemia with dystonia 1 (HMNDYT1) is characterized by the following:

  1. A movement disorder resulting from manganese accumulation in the basal ganglia

  2. Whole-blood manganese concentrations that often exceed 2000 nmol/L (normal: <320 nmol/L)

  3. Polycythemia

  4. Hepatomegaly with variable hepatic fibrosis/cirrhosis

Neurologic findings can manifest in childhood (ages 2-15 years) as four-limb dystonia, leading to a characteristic high-stepping gait ("cock-walk gait"), dysarthria, fine tremor, and bradykinesia or on occasion spastic paraplegia; or in adulthood as parkinsonism (shuffling gait, rigidity, bradykinesia, hypomimia, and monotone speech) unresponsive to L-dopa treatment.

Diagnosis/testing: The diagnosis of HMNDYT1 is established in a proband with suggestive findings and biallelic pathogenic variants in SLC30A10 identified by molecular genetic testing.

Management: Treatment of manifestations: Regular chelation therapy with intravenous disodium calcium edetate improves blood manganese levels and neurologic findings and halts liver disease. In addition, supplementation with oral iron therapy (despite normal serum iron levels) can reduce blood manganese levels and resolve polycythemia. The potential for complications from chelation therapy and/or iron supplementation can be lessened by careful monitoring. Physical therapy (to prevent contractures and maintain ambulation), occupational therapy, and/or speech therapy and use of adaptive aids and assistive communication devices are recommended. Progressive dystonia may necessitate a gastrostomy tube for adequate nutrition and a tracheostomy may be needed to prevent aspiration pneumonia.

Prevention of primary manifestations: Chelation therapy and iron supplementation may prevent primary disease manifestations in affected asymptomatic sibs.

Agents/circumstances to avoid: Foods very high in manganese: cloves; saffron; nuts; mussels; dark chocolate; and pumpkin, sesame, and sunflower seeds.

Evaluation of relatives at risk: Because chelation therapy and iron supplementation could prevent primary disease manifestations in affected asymptomatic individuals, it is recommended that at-risk sibs of a proband be evaluated either by molecular genetic testing (if the pathogenic variants in the family are known) or by periodic monitoring of whole-blood manganese concentration and hemoglobin.

Genetic counseling: HMNDYT1 is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for an SLC30A10 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of inheriting neither of the familial pathogenic variants. Once the SLC30A10 pathogenic variants have been identified in an affected family member, carrier testing for at-risk family members and prenatal and preimplantation genetic testing are possible.

Publication types

  • Review