Differences in MPS I and MPS II Disease Manifestations.
Differences in MPS I and MPS II Disease Manifestations.
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DOI：
10.3390/ijms22157888
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发表时间：
2021-07-23
影响因子：
5.6
通讯作者：
McIvor RS
中科院分区：
文献类型：
--
作者：
Hampe CS;Yund BD;Orchard PJ;Lund TC;Wesley J;McIvor RS
I 型和 II 型粘多糖贮积症 (MPS) 是两种与糖胺聚糖分解代谢紊乱相关的密切相关的溶酶体贮积病。在 MPS II 中，硫酸乙酰肝素 (HS) 和硫酸皮肤素 (DS) 降解的第一步因溶酶体酶艾杜糖醛酸 2-硫酸酯酶 (IDS) 的缺乏而受阻，而在 MPS I 中，第二步的受阻是因艾杜糖醛酸酶 (IDUA) 的缺乏所致。随后 HS 和 DS 的积累导致溶酶体肥大和细胞内溶酶体数量增加，并影响细胞功能，如细胞粘附、内吞作用、不同分子的细胞内运输、细胞内离子平衡和炎症。 MPS I 和 II 的特征性表型表现包括骨骼疾病，表现为身材矮小、腹股沟和脐疝、脑积水、听力损失、面部特征粗糙、腹部突出伴肝脾肿大，以及伴有不同功能问题的神经系统受累。然而，一些表现是疾病特异性的，包括 MPS I 中的角膜混浊、MPS II 中的表皮表现以及行为问题的严重性和性质的差异。这些表型差异似乎与 DS 和 HS 之间的不同比例及其硫酸化水平有关。 MPS I 的特点是 DS/HS 水平较高和硫酸化水平较低，而 MPS II 中 HS 水平高于 DS 水平且硫酸化水平较高。 DS 在角膜中的大量存在及其参与胶原原纤维的排列可能会导致 MPS I 中普遍存在角膜混浊，但在 MPS II 中则不然。神经系统参与的差异可能是由于 MPS II 中 HS 水平升高所致，因为 HS 参与神经元发育。目前 MPS II 患者的治疗选择通常仅限于酶替代疗法 (ERT)。虽然 ERT 对呼吸和心肺功能有有益作用，并可延长患者的寿命，但它不会显着影响中枢神经系统的表现，可能是因为酶无法以足够的水平通过血脑屏障。因此，许多实验性疗法旨在将 IDS 输送至中枢神经系统，以试图防止患者的神经认知能力下降。
Mucopolysaccharidosis (MPS) type I and II are two closely related lysosomal storage diseases associated with disrupted glycosaminoglycan catabolism. In MPS II, the first step of degradation of heparan sulfate (HS) and dermatan sulfate (DS) is blocked by a deficiency in the lysosomal enzyme iduronate 2-sulfatase (IDS), while, in MPS I, blockage of the second step is caused by a deficiency in iduronidase (IDUA). The subsequent accumulation of HS and DS causes lysosomal hypertrophy and an increase in the number of lysosomes in cells, and impacts cellular functions, like cell adhesion, endocytosis, intracellular trafficking of different molecules, intracellular ionic balance, and inflammation. Characteristic phenotypical manifestations of both MPS I and II include skeletal disease, reflected in short stature, inguinal and umbilical hernias, hydrocephalus, hearing loss, coarse facial features, protruded abdomen with hepatosplenomegaly, and neurological involvement with varying functional concerns. However, a few manifestations are disease-specific, including corneal clouding in MPS I, epidermal manifestations in MPS II, and differences in the severity and nature of behavioral concerns. These phenotypic differences appear to be related to different ratios between DS and HS, and their sulfation levels. MPS I is characterized by higher DS/HS levels and lower sulfation levels, while HS levels dominate over DS levels in MPS II and sulfation levels are higher. The high presence of DS in the cornea and its involvement in the arrangement of collagen fibrils potentially causes corneal clouding to be prevalent in MPS I, but not in MPS II. The differences in neurological involvement may be due to the increased HS levels in MPS II, because of the involvement of HS in neuronal development. Current treatment options for patients with MPS II are often restricted to enzyme replacement therapy (ERT). While ERT has beneficial effects on respiratory and cardiopulmonary function and extends the lifespan of the patients, it does not significantly affect CNS manifestations, probably because the enzyme cannot pass the blood–brain barrier at sufficient levels. Many experimental therapies, therefore, aim at delivery of IDS to the CNS in an attempt to prevent neurocognitive decline in the patients.
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影响因子：
2.9
作者：
Billings PC;Pacifici M
通讯作者：
Pacifici M
影响因子：
3.8
作者：
Boado, Ruben J.;Hui, Eric Ka-Wai;Pardridge, William M.
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DOI：
10.1083/jcb.200106075
发表时间：
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期刊：
The Journal of cell biology
影响因子：
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通讯作者：
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3.8
作者：
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影响因子：
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作者：
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