Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder characterized by α-L-iduronidase deficiency. Patients present with a broad spectrum of disease severity ranging from the most severe phenotype (Hurler) with devastating neurocognitive decline, bone disease and early death to intermediate (Hurler-Scheie) and more attenuated (Scheie) phenotypes, with a normal life expectancy. The most severely affected patients are preferably treated with hematopoietic stem cell transplantation, which halts the neurocognitive decline. Patients with more attenuated phenotypes are treated with enzyme replacement therapy. There are several challenges to be met in the treatment of MPS I patients. First, to optimize outcome, early recognition of the disease and clinical phenotype is needed to guide decisions on therapeutic strategies. Second, there is thus far no effective treatment available for MPS I bone disease. The pathophysiological mechanisms behind bone disease are largely unknown, limiting the development of effective therapeutic strategies. This article is a state of the art that comprehensively discusses three of the most urgent open issues in MPS I: early diagnosis of MPS I patients, pathophysiology of MPS I bone disease, and emerging therapeutic strategies for MPS I bone disease.

中文翻译：

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MPS I：早期诊断，骨病和治疗，我们现在在哪里？

I型粘多糖贮积症（MPS I）是一种以α-L-艾杜糖苷酶缺乏为特征的溶酶体贮积症。患者表现出广泛的疾病严重程度，从具有破坏性神经认知能力下降、骨病和早期死亡的最严重表型 (Hurler) 到具有正常预期寿命的中间 (Hurler-Scheie) 和更减毒 (Scheie) 表型。受影响最严重的患者最好接受造血干细胞移植治疗，从而阻止神经认知能力下降。具有更多减毒表型的患者接受酶替代疗法治疗。在 MPS I 患者的治疗中，有几个挑战需要解决。首先，为了优化结果，需要早期识别疾病和临床表型来指导治疗策略的决策。第二，迄今为止，对于 MPS I 骨病尚无有效的治疗方法。骨病背后的病理生理机制在很大程度上是未知的，限制了有效治疗策略的发展。本文全面讨论了 MPS I 中三个最紧迫的未解决问题：MPS I 患者的早期诊断、MPS I 骨病的病理生理学以及 MPS I 骨病的新兴治疗策略。