Stem Cell & Neurotherapies Laboratory, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
Drug Delivery Group, Institute of Pharmaceutical Science, King's College London, London, UK.
Mol Genet Metab. 2018 Dec;125(4):322-331. doi: 10.1016/j.ymgme.2018.08.003. Epub 2018 Aug 10.
Mucopolysaccharidosis (MPS) disorders are caused by deficiencies in lysosomal enzymes, leading to impaired glycosaminoglycan (GAG) degradation. The resulting GAG accumulation in cells and connective tissues ultimately results in widespread tissue and organ dysfunction. The seven MPS types currently described are heterogeneous and progressive disorders, with somatic and neurological manifestations depending on the type of accumulating GAG. Heparan sulfate (HS) is one of the GAGs stored in patients with MPS I, II, and VII and the main GAG stored in patients with MPS III. These disorders are associated with significant central nervous system (CNS) abnormalities that can manifest as impaired cognition, hyperactive and/or aggressive behavior, epilepsy, hydrocephalus, and sleeping problems. This review discusses the anatomical and pathophysiological CNS changes accompanying HS accumulation as well as the mechanisms believed to cause CNS abnormalities in MPS patients. The content of this review is based on presentations and discussions on these topics during a meeting on the brain in MPS attended by an international group of MPS experts.
黏多糖贮积症（MPS）是由溶酶体酶缺乏引起的，导致糖胺聚糖（GAG）降解受损。细胞和结缔组织中 GAG 的积累最终导致广泛的组织和器官功能障碍。目前描述的七种 MPS 类型是异质性和进行性疾病，根据积累 GAG 的类型，有躯体和神经表现。硫酸乙酰肝素（HS）是 MPS I、II 和 VII 患者中储存的 GAG 之一，也是 MPS III 患者中主要储存的 GAG。这些疾病与中枢神经系统（CNS）的显著异常有关，表现为认知障碍、多动和/或攻击性行为、癫痫、脑积水和睡眠问题。这篇综述讨论了伴随 HS 积累的 CNS 解剖和病理生理学变化，以及据信导致 MPS 患者 CNS 异常的机制。这篇综述的内容基于在 MPS 脑会议上关于这些主题的演讲和讨论，该会议由一群国际 MPS 专家参加。
