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

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.

Hypermanganesemia Induced Chorea and Cognitive Decline in a Tea Seller

“…The serum manganese level in our patient was found to be similarly high compared to other recently reported cases of hypermanganesemia, i.e. above 3000 nmol/L, which was far beyond the reference value (less than 320 nmol/L) [4,5,7,10].…”

“…Manganese affects neurons of striatum (caudate nucleus, putamen and nucleus accumbens), globus pallidus and substantia nigra, resulting in motor dysfunction with associated psychiatric and cognitive features, collectively known as "manganism" [2][3][4]. Hypermanganesemia due to mutations in SLC30A10, SLC39A14, and SLC39A8 presents at an early age with predominantly dystonia, gait disturbance, blood dyscrasias, and hepatic dysfunction [5][6][7][8][9][10][11]. On the other side, common causes of acquired hypermanganesemia are dietary exposure (food and drinking water), inhalational exposure, total parenteral nutrition and recreational drug use, among others [12][13][14][15].…”

Clinical Profile and Treatment Outcomes of Hypermanganesemia with Dystonia 1 and 2 among 27 Indian Children

“…In both conditions, pathognomonic magnetic resonance imaging (MRI) features include T1‐weighted hyperintensities in basal ganglia, midbrain, dorsal pons, and medulla with characteristic sparing of the ventral pons 2,3,5–8 . Forty‐five cases with SLC30A10 4,9–12 and 18 with SLC39A14 mutations have been described 4,13,14 …”

Hypermanganesemia with Dystonia Type 2: A Potentially Treatable Neurodegenerative Disorder: A Case Series in a Tertiary University Hospital

“…Patients with hypermanganesemia also have characteristic brain imaging findings, including high T1 signal intensity in the basal ganglia, specifically the globus pallidus, and less commonly in the cerebellum and brainstem [ 6 , 7 , 8 ]. Although these signal changes can improve with chelation therapy, they have been reported to persist despite treatment [ 4 , 9 ]. The pallidal index, which is defined as the ratio between the signal intensity in the globus pallidus and the subcortical frontal white matter on axial T1-weighted magnetic resonance imaging (MRI), is significantly higher in patients with hypermanganesemia and can be used as an indirect and noninvasive tool to assess disease progression [ 4 ].…”