Mucopolysaccharidosis type I (MPS I) is a rare autosomal recessive inherited disease, caused by deficiency of the enzyme α-L-iduronidase, resulting in accumulation of the glycosaminoglycans (GAGs) dermatan and heparan sulfate in organs and tissues. If untreated, patients with the severe phenotype die within the first decade of life. Early diagnosis is crucial to prevent the development of fatal disease manifestations, prominently cardiac and respiratory disease, as well as cognitive impairment. However, the initial symptoms are nonspecific and impede early diagnosis. This review discusses common phenotypic manifestations in the order in which they develop. Similarities and differences in the three animal models for MPS I are highlighted. Earliest symptoms, which present during the first 6 months of life, include hernias, coarse facial features, recurrent rhinitis and/or upper airway obstructions in the absence of infection, and thoracolumbar kyphosis. During the next 6 months, loss of hearing, corneal clouding, and further musculoskeletal dysplasias develop. Finally, late manifestations including lower airway obstructions and cognitive decline emerge. Cardiac symptoms are common in MPS I and can develop in infancy. The underlying pathogenesis is in the intra- and extracellular accumulation of partially degraded GAGs and infiltration of cells with enlarged lysosomes causing tissue expansion and bone deformities. These interfere with the proper arrangement of collagen fibrils, disrupt nerve fibers, and cause devastating secondary pathophysiological cascades including inflammation, oxidative stress, and other disruptions to intracellular and extracellular homeostasis. A greater understanding of the natural history of MPS I will allow early diagnosis and timely management of the disease facilitating better treatment outcomes.

中文翻译：

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I型粘多糖贮积病：自然史和分子病理学的回顾。

I型粘多糖贮积病（MPS I）是一种罕见的常染色体隐性遗传病，由α-L-异戊糖苷酶缺乏引起，导致皮肤组织中糖胺聚糖（GAGs）皮肤素和硫酸乙酰肝素的积累。如果不进行治疗，则具有严重表型的患者会在生命的头十年内死亡。早期诊断对于预防致命性疾病表现（主要是心脏和呼吸道疾病）以及认知障碍的发展至关重要。然而，最初的症状是非特异性的，并妨碍早期诊断。这篇评论讨论了常见的表型发展的顺序。强调了MPS I的三种动物模型的异同。生命初期的6个月内出现的最早症状包括疝气，面部粗糙，在没有感染的情况下复发性鼻炎和/或上呼吸道阻塞，以及胸腰椎后凸畸形。在接下来的6个月中，会出现听力丧失，角膜混浊和进一步的肌肉骨骼发育异常。最后，出现晚期症状，包括下呼吸道阻塞和认知能力下降。心脏症状在MPS I中很常见，并可能在婴儿期发展。潜在的发病机理是部分降解的GAG在细胞内和细胞外的积累，以及溶酶体扩大导致细胞的浸润，从而引起组织扩张和骨骼畸形。这些会干扰胶原纤维的正确排列，破坏神经纤维，并导致毁灭性的继发性病理生理级联反应，包括炎症，氧化应激以及对细胞内和细胞外稳态的其他破坏。