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Abstract：
BACKGROUND: Mucopolysaccharidosis (MPS) II is a rare, X-linked lysosomal storage disease. Approximately two-thirds of patients have central nervous system involvement with some demonstrating progressive cognitive impairment (neuronopathic disease). The natural history of cognitive and adaptive function in patients with MPS II is not well-defined. This 2-year, prospective, observational study evaluated the neurodevelopmental trajectories of boys with MPS II aged ≥ 2 years and < 18 years.
RESULTS: Overall, 55 patients were enrolled. At baseline, mean (standard deviation [SD]) age was 5.60 (3.32) years; all patients were receiving intravenous idursulfase. Cognitive and adaptive function were assessed using the Differential Ability Scales, Second Edition (DAS-II) General Conceptual Ability (GCA) and the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Adaptive Behavior Composite (ABC) scores, respectively. Baseline mean (SD) DAS-II GCA and VABS-II ABC scores were 78.4 (19.11) and 83.7 (14.22), respectively, indicating low cognitive function and moderately low adaptive behavior. Over 24 months, modest deteriorations in mean (SD) scores were observed for DAS-II GCA (-3.8 [12.7]) and VABS-II ABC (-2.0 [8.07]). Changes in DAS-II GCA scores varied considerably, and data suggested the existence of four potential patient subgroups: (1) patients with marked early impairment and rapid subsequent decline, (2) patients with marked early impairment then stabilization, (3) patients with mild early impairment then stabilization, and (4) patients without impairment who remained stable. Subgroup analyses revealed numerically greater DAS-II GCA score reductions from baseline in patients aged < 7 years at baseline (vs. those aged ≥ 7 years) and in patients with DAS-II GCA scores ≤ 70 at baseline (vs. those with scores > 70); between-group differences were nonsignificant. No clear subgroups or patterns were identified for individual changes in VABS-II ABC scores. In total, 49 patients (89.1%) reported ≥ 1 adverse event (AE) and nine patients (16.4%) reported serious AEs.
CONCLUSIONS: Some patients with MPS II had rapid declines in cognitive ability, whereas others remained relatively stable after an initial decline. These insights provide a basis for more detailed analyses of different patient subgroups, which may enhance the definition and understanding of factors that influence cognitive and adaptive function in MPS II.
BACKGROUND: ClinicalTrials.gov, NCT01822184. Registered retrospectively: April 2, 2013.
RESULTS: Overall, 55 patients were enrolled. At baseline, mean (standard deviation [SD]) age was 5.60 (3.32) years; all patients were receiving intravenous idursulfase. Cognitive and adaptive function were assessed using the Differential Ability Scales, Second Edition (DAS-II) General Conceptual Ability (GCA) and the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Adaptive Behavior Composite (ABC) scores, respectively. Baseline mean (SD) DAS-II GCA and VABS-II ABC scores were 78.4 (19.11) and 83.7 (14.22), respectively, indicating low cognitive function and moderately low adaptive behavior. Over 24 months, modest deteriorations in mean (SD) scores were observed for DAS-II GCA (-3.8 [12.7]) and VABS-II ABC (-2.0 [8.07]). Changes in DAS-II GCA scores varied considerably, and data suggested the existence of four potential patient subgroups: (1) patients with marked early impairment and rapid subsequent decline, (2) patients with marked early impairment then stabilization, (3) patients with mild early impairment then stabilization, and (4) patients without impairment who remained stable. Subgroup analyses revealed numerically greater DAS-II GCA score reductions from baseline in patients aged < 7 years at baseline (vs. those aged ≥ 7 years) and in patients with DAS-II GCA scores ≤ 70 at baseline (vs. those with scores > 70); between-group differences were nonsignificant. No clear subgroups or patterns were identified for individual changes in VABS-II ABC scores. In total, 49 patients (89.1%) reported ≥ 1 adverse event (AE) and nine patients (16.4%) reported serious AEs.
CONCLUSIONS: Some patients with MPS II had rapid declines in cognitive ability, whereas others remained relatively stable after an initial decline. These insights provide a basis for more detailed analyses of different patient subgroups, which may enhance the definition and understanding of factors that influence cognitive and adaptive function in MPS II.
BACKGROUND: ClinicalTrials.gov, NCT01822184. Registered retrospectively: April 2, 2013.
摘要：
背景：粘多糖贮积症（MPS）II是一种罕见的，X连锁溶酶体贮积病。大约三分之二的患者有中枢神经系统受累，一些表现为进行性认知障碍（神经病性疾病）。MPSII患者的认知和适应功能的自然史尚不明确。这两年,prospective,观察性研究评估了年龄≥2岁和<18岁的MPSII男孩的神经发育轨迹。
结果：总体而言，55例患者入组。在基线,平均(标准差[SD])年龄为5.60(3.32)岁;所有患者均接受静脉注射艾杜磺酶。使用差异能力量表评估认知和适应功能，第二版(DAS-II)一般概念能力(GCA)和Vineland自适应行为量表，第二版(VABS-II)自适应行为综合(ABC)评分，分别。基线平均（SD）DAS-IIGCA和VABS-IIABC评分分别为78.4（19.11）和83.7（14.22），分别,表明低认知功能和中度低适应行为。超过24个月,观察到DAS-IIGCA(-3.8[12.7])和VABS-IIABC(-2.0[8.07])的平均(SD)评分适度恶化.DAS-IIGCA分数的变化差异很大，和数据表明存在四个潜在的患者亚组：（1）具有明显的早期损害和随后的快速下降的患者，（2）患者有明显的早期损害，然后稳定，（3）患者轻度早期损害，然后稳定，和（4）患者无损伤谁保持稳定。亚组分析显示，在基线时年龄<7岁的患者中，DAS-IIGCA评分比基线降低的数值更大（与年龄≥7岁的患者）和基线时DAS-IIGCA评分≤70的患者（与评分>70）；组间差异无统计学意义。对于VABS-IIABC评分的个体变化，未发现明确的亚组或模式。总的来说,49例患者（89.1%）报告≥1次不良事件（AE），9例患者（16.4%）报告严重AE。
结论：一些MPSII患者的认知能力迅速下降，而其他人在最初下降后保持相对稳定。这些见解为更详细地分析不同的患者亚组提供了基础，这可能会增强对影响MPSII认知和适应功能的因素的定义和理解。
背景：ClinicalTrials.gov，NCT01822184。回顾性注册：2013年4月2日。
结果：总体而言，55例患者入组。在基线,平均(标准差[SD])年龄为5.60(3.32)岁;所有患者均接受静脉注射艾杜磺酶。使用差异能力量表评估认知和适应功能，第二版(DAS-II)一般概念能力(GCA)和Vineland自适应行为量表，第二版(VABS-II)自适应行为综合(ABC)评分，分别。基线平均（SD）DAS-IIGCA和VABS-IIABC评分分别为78.4（19.11）和83.7（14.22），分别,表明低认知功能和中度低适应行为。超过24个月,观察到DAS-IIGCA(-3.8[12.7])和VABS-IIABC(-2.0[8.07])的平均(SD)评分适度恶化.DAS-IIGCA分数的变化差异很大，和数据表明存在四个潜在的患者亚组：（1）具有明显的早期损害和随后的快速下降的患者，（2）患者有明显的早期损害，然后稳定，（3）患者轻度早期损害，然后稳定，和（4）患者无损伤谁保持稳定。亚组分析显示，在基线时年龄<7岁的患者中，DAS-IIGCA评分比基线降低的数值更大（与年龄≥7岁的患者）和基线时DAS-IIGCA评分≤70的患者（与评分>70）；组间差异无统计学意义。对于VABS-IIABC评分的个体变化，未发现明确的亚组或模式。总的来说,49例患者（89.1%）报告≥1次不良事件（AE），9例患者（16.4%）报告严重AE。
结论：一些MPSII患者的认知能力迅速下降，而其他人在最初下降后保持相对稳定。这些见解为更详细地分析不同的患者亚组提供了基础，这可能会增强对影响MPSII认知和适应功能的因素的定义和理解。
背景：ClinicalTrials.gov，NCT01822184。回顾性注册：2013年4月2日。
