Peck Sun H, Casal Margret L, Malhotra Neil R, Ficicioglu Can, Smith Lachlan J
Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, United States; Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, United States.
Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, United States.
Mol Genet Metab. 2016 Aug;118(4):232-43. doi: 10.1016/j.ymgme.2016.06.002. Epub 2016 Jun 4.
The mucopolysaccharidoses (MPS) are a family of lysosomal storage disorders characterized by deficient activity of enzymes that degrade glycosaminoglycans (GAGs). Skeletal disease is common in MPS patients, with the severity varying both within and between subtypes. Within the spectrum of skeletal disease, spinal manifestations are particularly prevalent. Developmental and degenerative abnormalities affecting the substructures of the spine can result in compression of the spinal cord and associated neural elements. Resulting neurological complications, including pain and paralysis, significantly reduce patient quality of life and life expectancy. Systemic therapies for MPS, such as hematopoietic stem cell transplantation and enzyme replacement therapy, have shown limited efficacy for improving spinal manifestations in patients and animal models. Therefore, there is a pressing need for new therapeutic approaches that specifically target this debilitating aspect of the disease. In this review, we examine how pathological abnormalities affecting the key substructures of the spine - the discs, vertebrae, odontoid process and dura - contribute to the progression of spinal deformity and symptomatic compression of neural elements. Specifically, we review current understanding of the underlying pathophysiology of spine disease in MPS, how the tissues of the spine respond to current clinical and experimental treatments, and discuss future strategies for improving the efficacy of these treatments.
黏多糖贮积症（MPS）是一类溶酶体贮积病，其特征是降解糖胺聚糖（GAGs）的酶活性不足。骨骼疾病在MPS患者中很常见，严重程度在各亚型内和各亚型间有所不同。在骨骼疾病范围内，脊柱表现尤为普遍。影响脊柱亚结构的发育和退行性异常可导致脊髓和相关神经元件受压。由此产生的神经并发症，包括疼痛和瘫痪，会显著降低患者的生活质量和预期寿命。MPS的全身治疗，如造血干细胞移植和酶替代疗法，在改善患者和动物模型的脊柱表现方面疗效有限。因此，迫切需要新的治疗方法来专门针对该疾病这一使人衰弱的方面。在本综述中，我们研究了影响脊柱关键亚结构——椎间盘、椎体、齿突和硬脑膜——的病理异常如何导致脊柱畸形的进展和神经元件的症状性受压。具体而言，我们综述了目前对MPS脊柱疾病潜在病理生理学的理解、脊柱组织对当前临床和实验治疗的反应，并讨论了提高这些治疗疗效的未来策略。
