A case of dystonia with polycythemia and hypermanganesemia caused by SLC30A10 mutation: a treatable inborn error of manganese metabolism
| Autor: | Marziyeh Mojbafan, Soudabeh Hosseini, Elham Zarei, Saba Hemmati, Azita Tavasoli, Khadije Arjmandi Rafsanjani |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
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 |
| Zdroj: | BMC Pediatrics BMC Pediatrics, Vol 19, Iss 1, Pp 1-6 (2019) |
| ISSN: | 1471-2431 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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