Spiridigliozzi Gail A, Keeling Lori A, Stefanescu Mihaela, Li Cindy, Austin Stephanie, Kishnani Priya S
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA.
Department of Psychology and Neuroscience, Duke University, Durham, NC, USA.
Mol Genet Metab. 2017 Jun;121(2):127-137. doi: 10.1016/j.ymgme.2017.04.014. Epub 2017 May 1.
This study examines the long-term cognitive and academic outcomes of 11 individuals with infantile onset Pompe disease (IOPD) (median age=11years, 1month, range=5years, 6months through 17years of age) treated with enzyme replacement therapy from an early age. All participants (7 males, 4 females) were administered individual intelligence tests (Wechsler or Leiter scales or both), a measure of their academic skill levels (Woodcock-Johnson Tests of Achievement), and a screening measure of visual-motor integration ability (Beery-Buktenica). Consistent with our earlier findings, median IQ scores for the entire group on the Wechsler (median=84) and Leiter (median=92) scales continue to fall at the lower end of the average range compared to same-aged peers. The median scores for the group on a measure of visual-motor integration (median=76), visual perception (median=74) and motor coordination (median=60) were below average. Two distinct subgroups emerged based on participants' average or below average performance on the majority of academic subtests. Those participants with below average academic skills (n=6) demonstrated average nonverbal cognitive abilities on the Leiter, but had weaknesses in speech and language skills and greater medical involvement. Their profiles were more consistent with a learning disability diagnosis than an intellectual disability. Two of these participants showed a significant decline (15 and 23 points, respectively) on repeated Wechsler scales, but one continued to earn average scores on the Leiter scales where the verbal and motor demands are minimal. Participants with average academic skills (n=5) demonstrated average cognitive abilities (verbal and nonverbal) on the Wechsler scales and less medical involvement. Their speech and language skills appeared to be more intact. However, both groups earned below average median scores on the Beery-Buktenica motor coordination task. This study highlights the importance of using appropriate tests to capture both verbal and nonverbal abilities, considering each individual's motor skills, speech and language abilities, hearing status and native language. This will allow for a more accurate assessment of whether there is a learning disability or an intellectual disability. Long-term outcomes may be related to the stability of an individual's expressive and/or receptive language abilities over time. Changes in the speech and language domain may account for the decline in IQ observed in some IOPD long-term survivors, reflecting a learning disability rather than a decline in overall cognition or an intellectual disability. These observations, in conjunction with neuroimaging, will further our understanding of the neurocognitive profile of long-term IOPD survivors.
本研究考察了11例自幼接受酶替代疗法治疗的婴儿型庞贝病（IOPD）患者（中位年龄 = 11岁1个月，范围 = 5岁6个月至17岁）的长期认知和学业成果。所有参与者（7名男性，4名女性）均接受了个体智力测试（韦氏或莱特量表或两者皆有）、学业技能水平测量（伍德库克 - 约翰逊成就测验）以及视觉 - 运动整合能力筛查测量（贝里 - 布克滕尼卡测试）。与我们早期的研究结果一致，与同龄同龄人相比，整个组在韦氏量表（中位数 = 84）和莱特量表（中位数 = 92）上的智商中位数分数仍处于平均范围的较低端。该组在视觉 - 运动整合测量（中位数 = 76）、视觉感知（中位数 = 74）和运动协调（中位数 = 60）方面的中位数分数均低于平均水平。根据参与者在大多数学业子测试中的平均或低于平均表现，出现了两个不同的亚组。那些学业技能低于平均水平的参与者（n = 6）在莱特量表上表现出平均的非言语认知能力，但在言语和语言技能方面存在弱点，且医疗介入较多。他们的情况更符合学习障碍的诊断，而非智力障碍。其中两名参与者在重复的韦氏量表上出现了显著下降（分别下降了15分和23分），但有一名参与者在言语和运动要求最低的莱特量表上继续获得平均分数。学业技能平均的参与者（n = 5）在韦氏量表上表现出平均的认知能力（言语和非言语），且医疗介入较少。他们的言语和语言技能似乎更完整。然而，两组在贝里 - 布克滕尼卡运动协调任务中的中位数分数均低于平均水平。本研究强调了使用适当测试来获取言语和非言语能力的重要性，同时要考虑到每个人的运动技能、言语和语言能力、听力状况以及母语。这将有助于更准确地评估是否存在学习障碍或智力障碍。长期结果可能与个体表达性和/或接受性语言能力随时间的稳定性有关。言语和语言领域的变化可能解释了一些IOPD长期存活者中观察到的智商下降，这反映的是学习障碍，而非整体认知能力下降或智力障碍。这些观察结果与神经影像学相结合，将加深我们对IOPD长期存活者神经认知特征的理解。
