The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA.
Hospital Nacional de Pediatría J. P. Garrahan, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
Am J Med Genet A. 2022 Oct;188(10):2941-2951. doi: 10.1002/ajmg.a.62910. Epub 2022 Jul 23.
Mucopolysaccharidosis Type I (MPS I) is caused by deficiency of α-L-iduronidase. Short stature and growth deceleration are common in individuals with the attenuated MPS I phenotype. Study objectives were to assess growth in individuals with attenuated MPS I enrolled in The MPS I Registry while untreated and after initiation of enzyme replacement therapy (ERT) with laronidase (recombinant human iduronidase). Individuals in the MPS I Registry with at least one observation for height and assigned attenuated MPS I phenotype as of September 2020 were included. The cohort included 142 males and 153 females 2-18 years of age. Age and sex adjusted standardized height-for-age z-scores during the natural history and ERT-treatment periods were assessed using linear mixed model repeated measures analyses. Growth curves were estimated during both periods and compared to standard growth charts from the Center for Disease Control (CDC). There was a significantly slower decline in height z-scores with age during the ERT-treated period compared to the natural history period. Estimated average height z-scores in the ERT-treatment versus the natural history period at age 10 were -2.4 versus -3.3 in females and -1.4 versus -2.9 in males (females first treated 3 year; males <4.1 year). While median height remained below CDC standards during both the natural history and ERT-treated periods for individuals with attenuated MPS I, laronidase ERT was associated with slower declines in height z-scores.
黏多糖贮积症 I 型(MPS I)是由α-L-艾杜糖苷酸酶缺乏引起的。在表型减弱的 MPS I 个体中,身材矮小和生长减速是常见的。研究目的是评估在未经治疗和开始使用拉罗尼酶(重组人艾杜糖苷酸酶)进行酶替代治疗(ERT)的情况下,入组 MPS I 登记处的表型减弱的 MPS I 个体的生长情况。截至 2020 年 9 月,MPS I 登记处至少有一次身高观察结果且被分配为表型减弱的 MPS I 的个体被纳入研究。该队列包括 142 名男性和 153 名女性,年龄为 2-18 岁。使用线性混合模型重复测量分析评估自然史和 ERT 治疗期间的年龄和性别调整标准化身高年龄 z 评分。在两个时期都估计了生长曲线,并与疾病控制与预防中心(CDC)的标准生长图表进行了比较。与自然史期间相比,ERT 治疗期间身高 z 评分随年龄的下降速度明显较慢。ERT 治疗与自然史期间 10 岁时女性的平均身高 z 评分分别为-2.4 和-3.3,男性分别为-1.4 和-2.9(女性首次治疗 3 岁;男性<4.1 岁)。虽然在自然史和 ERT 治疗期间,表型减弱的 MPS I 个体的中位数身高仍低于 CDC 标准,但拉罗尼酶 ERT 与身高 z 评分下降速度较慢相关。