Although acquired manganese neurotoxicity has been widely reported since its first description in 1837 and is popularly referred to as “manganism,” inherited disorders of manganese homeostasis have received the first genetic signature as recently as 2012. These disorders, predominantly described in children and adolescents, involve mutations in three manganese transporter genes, i.e., SLC30A10 and SLC39A14 which lead to manganese overload, and SLC39A8, which leads to manganese deficiency. Both disorders of inherited hypermanganesemia typically exhibit dystonia and parkinsonism with relatively preserved cognition and are differentiated by the occurrence of polycythemia and liver involvement in the SLC30A10-associated condition. Mutations in SLC39A8 lead to a congenital disorder of glycosylation which presents with developmental delay, failure to thrive, intellectual impairment, and seizures due to manganese deficiency. Chelation with iron supplementation is the treatment of choice in inherited hypermanganesemia. In this review, we highlight the pathognomonic clinical, laboratory, imaging features and treatment modalities for these rare disorders.


中文翻译：

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遗传性锰疾病和大脑：神经病学家需要知道什么


尽管自1837年首次描述锰获得性神经毒性以来，锰的神经毒性得到了广泛报道，并且普遍被称为“锰中毒”，但锰稳态的遗传性疾病已于2012年获得了首个遗传特征。这些疾病主要描述于儿童和青少年中，涉及三个锰转运蛋白基因，即突变SLC30A10和SLC39A14从而导致锰超载和SLC39A8，从而导致缺锰。遗传性高锰血症的这两种疾病通常表现出肌张力障碍和帕金森氏病，认知相对保留，并且通过SLC30A10的红细胞增多症和肝脏受累来区分相关条件。SLC39A8中的突变会导致先天性糖基化疾病，表现为发育延迟、,壮成长，智力障碍和由于锰缺乏引起的癫痫发作。螯合铁补充剂是遗传性高锰血症的选择治疗方法。在这篇综述中，我们重点介绍了这些罕见疾病的病理学临床，实验室，影像学特征和治疗方式。