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Your search keyword '"Hypermanganesemia"' showing total 3 results
Start Over Descriptor "Hypermanganesemia" Publisher biomed central
3 results on '"Hypermanganesemia"'

1. Hypermanganesemia due to mutations in SLC39A14: further insights into Mn deposition in the central nervous system.

Author

Marti-Sanchez, L., Ortigoza-Escobar, J. D., Darling, A., Villaronga, M., Baide, H., Molero-Luis, M., Batllori, M., Vanegas, M. I., Muchart, J., Aquino, L., Artuch, R., Macaya, A., Kurian, M. A., and Dueñas, Pérez

Abstract

Background: The SLC39A14, SLC30A10 and SLC39A8 are considered to be key genes involved in manganese (Mn) homeostasis in humans. Mn levels in plasma and urine are useful tools for early recognition of these disorders. We aimed to explore further biomarkers of Mn deposition in the central nervous system in two siblings presenting with acute dystonia and hypermanganesemia due to mutations in SLC39A14. These biomarkers may help clinicians to establish faster and accurate diagnosis and to monitor disease progression after chelation therapy is administered.Results: A customized gene panel for movement disorders revealed a novel missense variant (c.311G > T; p.Ser104Ile) in SLC39A14 gene in two siblings presenting at the age of 10 months with acute dystonia and motor regression. Mn concentrations were analyzed using inductively coupled mass spectrometry in plasma and cerebrospinal fluid, disclosing elevated Mn levels in the index case compared to control patients. Surprisingly, Mn values were 3-fold higher in CSF than in plasma. We quantified the pallidal index, defined as the ratio between the signal intensity in the globus pallidus and the subcortical frontal white matter in axial T1-weighted MRI, and found significantly higher values in the SLC39A14 patient than in controls. These values increased over a period of 10 years, suggesting the relentless pallidal accumulation of Mn. Following genetic confirmation, a trial with the Mn chelator Na2CaEDTA led to a reduction in plasma Mn, zinc and selenium levels. However, parents reported worsening of cervical dystonia, irritability and sleep difficulties and chelation therapy was discontinued.Conclusions: Our study expands the very few descriptions of patients with SLC39A14 mutations. We report for the first time the elevation of Mn in CSF of SLC39A14 mutated patients, supporting the hypothesis that brain is an important organ of Mn deposition in SLC39A14-related disease. The pallidal index is an indirect and non-invasive method that can be used to rate disease progression on follow-up MRIs. Finally, we propose that patients with inherited defects of manganese transport should be initially treated with low doses of Na2CaEDTA followed by gradual dose escalation, together with a close monitoring of blood trace elements in order to avoid side effects. [ABSTRACT FROM AUTHOR]

Published
2018
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3. A case of dystonia with polycythemia and hypermanganesemia caused by SLC30A10 mutation: a treatable inborn error of manganese metabolism

Author

Marziyeh Mojbafan, Soudabeh Hosseini, Elham Zarei, Saba Hemmati, Azita Tavasoli, and Khadije Arjmandi Rafsanjani

Subjects
Proband, Male, medicine.medical_specialty, Cirrhosis, Ataxia, Genotype, Mutation, Missense, Case Report, Neuroimaging, Polycythemia, 03 medical and health sciences, Consanguinity, 0302 clinical medicine, Metabolic Diseases, 030225 pediatrics, Internal medicine, Exome Sequencing, medicine, Missense mutation, Humans, Point Mutation, 030212 general & internal medicine, Child, Cation Transport Proteins, Edetic Acid, Dystonia, Manganese, medicine.diagnostic_test, business.industry, SLC30A10, lcsh:RJ1-570, Brain, lcsh:Pediatrics, medicine.disease, Magnetic Resonance Imaging, Hyperintensity, Chelation Therapy, Endocrinology, Inborn error of metabolism, Hypermanganesemia, Pediatrics, Perinatology and Child Health, Serum iron, medicine.symptom, business, Iron Compounds
Abstract

Background Manganese is a critical trace element that not only has antioxidant properties, but also is essential for various metabolic pathways and neurotransmitters production. However, it can be toxic at high levels, particularly in the central nervous system. Manganese intoxication can be acquired, but an inherited form due to autosomal-recessive mutations in the SLC30A10 gene encoding a Mn transporter protein has also been reported recently. These mutations are associated with significant failure of manganese excretion and its storage in the liver, brain (especially basal ganglia), and other peripheral tissues, resulting in toxicity. Case presentation A 10-year-old boy from consanguineous parents presented with a history of progressive truncal instability, gait difficulty, and frequent falls for 2 months. He had dystonia, rigidity, ataxia, dysarthria, bradykinesia and a plethoric skin. Investigations showed polycythemia, low serum iron and ferritin levels, and increased total iron binding capacity. A brain MRI revealed symmetric hyperintensities in the basal ganglia and dentate nucleuses on TI images that were suggestive of brain metal deposition together with clinical manifestations. Serum calcium and copper levels were normal, while the manganese level was significantly higher than normal values. There was no history of environmental overexposure to manganese. Genetic testing showed a homozygous missense mutation in SLC30A10 (c.C1006T, p.His336Tyr) and Sanger sequencing confirmed a homozygous state in the proband and a heterozygous state in the parents. Regular treatment with monthly infusions of disodium calcium edetate and oral iron compounds resulted in decreased serum manganese and hemoglobin levels to normal values, significant resolution of MRI lesions, and partial improvement of neurological symptoms during 6 months of follow-up. Conclusion The syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia caused by SLC30A10 mutation is a treatable inherited metal deposition syndrome. The patient may only have pure neurological without hepatic manifestations. Although this is a rare and potentially fatal inborn error of metabolism, early diagnosis and continuous chelation therapy might improve the symptoms and prevent disease progression.

Published
2019

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