1.
A case of dystonia with polycythemia and hypermanganesemia caused by SLC30A10 mutation: a treatable inborn error of manganese metabolism.
Tavasoli, A, Arjmandi Rafsanjani, K, Hemmati, S, Mojbafan, M, Zarei, E, Hosseini, S
BMC pediatrics. 2019;(1):229
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.
2.
A current review for biological monitoring of manganese with exposure, susceptibility, and response biomarkers.
Kim, G, Lee, HS, Seok Bang, J, Kim, B, Ko, D, Yang, M
Journal of environmental science and health. Part C, Environmental carcinogenesis & ecotoxicology reviews. 2015;(2):229-54
Abstract
People can be easily exposed to manganese (Mn), the twelfth most abundant element, through various exposure routes. However, overexposure to Mn causes manganism, a motor syndrome similar to Parkinson disease, via interference of the several neurotransmitter systems, particularly the dopaminergic system in areas. At cellular levels, Mn preferentially accumulates in mitochondria and increases the generation of reactive oxygen species, which changes expression and activity of manganoproteins. Many studies have provided invaluable insights into the causes, effects, and mechanisms of the Mn-induced neurotoxicity. To regulate Mn exposure, many countries have performed biological monitoring of Mn with three major biomarkers: exposure, susceptibility, and response biomarkers. In this study, we review current statuses of Mn exposure via various exposure routes including food, high susceptible population, effects of genetic polymorphisms of metabolic enzymes or transporters (CYP2D6, PARK9, SLC30A10, etc.), alterations of the Mn-responsive proteins (i.e., glutamine synthetase, Mn-SOD, metallothioneins, and divalent metal trnsporter1), and epigenetic changes due to the Mn exposure. To minimize the effects of Mn exposure, further biological monitoring of Mn should be done with more sensitive and selective biomarkers.
3.
Relationship between dietary magnesium, manganese, and copper and metabolic syndrome risk in Korean adults: the Korea National Health and Nutrition Examination Survey (2007-2008).
Choi, MK, Bae, YJ
Biological trace element research. 2013;(1-3):56-66
Abstract
Recent studies have reported correlations between mineral intake and metabolic syndrome (MS), but accurate relationships and consistency in the results are difficult to confirm. Accordingly, this study aims to assess the dietary intakes of magnesium (Mg), manganese (Mn), and copper (Cu) to determine their relationship with MS. Data from a total of 5,136 adults (2,084 men, 3,052 women) was collected from the 2007-2008 Korea National Health and Nutrition Examination Survey (KNHANES), and the intakes of Mg, Mn, and Cu of the MS patients were compared with those of healthy adults. The relationship between the intakes of these minerals and the MS risks was analyzed. Diagnosis of MS was evaluated by the National Cholesterol Education Program's Adult Treatment Panel III (NCEP-ATP III) standards. Among all study subjects, 25.9 % (540 subjects) of the men and 24.5 % (748 subjects) of the women met diagnostic criteria for inclusion in the MS group. In the men, daily intakes of Mg and Cu in the MS group were significantly lower than those in control group, and in the women, daily intakes of energy, Mg, Mn, and Cu in the MS group were significantly lower than those of the control group. The women subjects with high blood pressure showed significantly lower intakes of Mg, Mn, and Cu than control subjects. In addition, in the women, the highest quartile of Mg and Cu was inversely associated with MS, but with adjustment were not maintained. However, in the postmenopausal women, MS was significant and inversely associated with the highest quartiles of Cu intake and the association remained significant after adjustments. Considering that MS incidence increases and dietary intake and nutrient density decrease with increasing age, and mineral intake is reduced accordingly, these results suggest that meal management with adequate mineral intake is advisable to control MS.
4.
[Chronic hepatic encephalopathy: the role of high serum manganese levels and its relation with basal ganglia lesions in nuclear magnetic resonance of the brain. Clinical case].
Miranda, M, Caballero, L
Revista medica de Chile. 2001;(9):1051-5
Abstract
Chronic hepatic encephalopathy (CHE) is a disabling complication of chronic liver failure and porto-systemic shunt. The pathogenesis of CHE remains unclear but increased levels of ammonia are a basic feature. Several clinical and experimental observations support a role for manganese (Mn) in the pathogenesis of this disorder. Increased blood levels of Mn have been described in patients with CHE and this could lead to its accumulation on the basal ganglia and characteristic hyperintensities of basal ganglia as seen on magnetic resonance imaging (MRI) of the brain. We report on the clinical features and characteristic radiologic findings of a patient who presented with the neurologic syndrome of CHE and who had very high blood levels of Mn in the absence of an occupational exposure to this metal. Our report supports the hypothesis that Mn has a role in the pathogenesis of CHE and also suggests that brain MRI is a useful marker of the brain metabolic repercussion due to CHE.