Fang Sherry, Clayton Peter T, Garg Divyani, Yoganathan Sangeetha, Zaki Maha S, Helgadottir Elin A, Palmadottir Vala K, Landry Maude, Gospe Sidney M, Mankad Kshitij, Bonifati Vincenzo, Sharma Suvasini, Tuschl Karin
Department of Metabolic Medicine, Great Ormond Street Hospital for Children, London, UK.
Department of Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, University College London, London, UK.
J Inherit Metab Dis. 2025 May;48(3):e70031. doi: 10.1002/jimd.70031.
Hypermanganesaemia with Dystonia 1 and 2 (HMNDYT1 and 2) are inherited, autosomal recessive disorders caused by pathogenic variants in the genes encoding the manganese transporters SLC30A10 and SLC39A14, respectively. Impaired hepatic and enterocytic manganese uptake (SLC39A14) and excretion (SLC30A10) lead to deposition of manganese in the basal ganglia resulting in childhood-onset dystonia-parkinsonism. HMNDYT1 is characterized by additional features due to manganese accumulation in the liver causing cirrhosis, polycythaemia, and depleted iron stores. High blood manganese levels and pathognomonic MRI brain appearances of manganese deposition resulting in T1 hyperintensity of the basal ganglia are diagnostic clues. Treatment is limited to chelation therapy and iron supplementation that can prevent disease progression. Due to their rarity, the awareness of the inherited manganese transporter defects is limited. Here, we provide consensus expert recommendations for the diagnosis and treatment of patients with HMNDYT1 and 2 in order to facilitate early diagnosis and optimize clinical outcome. These recommendations were developed through an evidence and consensus-based process led by a group of 13 international experts across the disciplines of metabolic medicine, neurology, hematology, genetics, and radiology, and address the clinical presentation, diagnostic investigations, principles of treatment, and monitoring of patients with HMNDYT1 and 2.
伴有肌张力障碍1型和2型的高锰血症（HMNDYT1和2）是分别由编码锰转运蛋白SLC30A10和SLC39A14的基因中的致病变异引起的常染色体隐性遗传病。肝脏和肠细胞对锰的摄取（SLC39A14）和排泄（SLC30A10）受损导致锰在基底神经节沉积，从而引起儿童期肌张力障碍 - 帕金森综合征。HMNDYT1的特征还包括因肝脏中锰蓄积导致的肝硬化、红细胞增多症和铁储备减少等其他症状。血锰水平升高以及基底神经节锰沉积导致T1高信号的典型MRI脑表现是诊断线索。治疗仅限于螯合疗法和铁补充，这可以预防疾病进展。由于它们较为罕见，对遗传性锰转运蛋白缺陷病的认识有限。在此，我们提供关于HMNDYT1和2患者诊断和治疗的专家共识建议，以促进早期诊断并优化临床结果。这些建议是由13位来自代谢医学、神经病学、血液学、遗传学和放射学等学科的国际专家通过基于证据和共识的过程制定的，涉及HMNDYT1和2患者的临床表现、诊断检查、治疗原则以及监测等方面。
