Patterson Catherine, Gold Anna, So Stephanie, Kahnami Leila, Dworsky-Fried Michaela, Mamak Eva, Rogers Alaine, Schulze Andreas, Ertl-Wagner Birgit, Ng Vicky, Avitzur Yaron
Department of Rehabilitation Services, The Hospital for Sick Children, Toronto, Ontario, Canada.
Department of Physical Therapy, University of Toronto, Toronto, Ontario, Canada.
J Inherit Metab Dis. 2025 Jan;48(1):e12785. doi: 10.1002/jimd.12785. Epub 2024 Aug 12.
This study describes the neurodevelopmental outcome of children with urea cycle disorders (UCD) and organic acidemias (OA) preliver transplant (LT), 1-year, and 3-years post-LT. We performed a retrospective chart review of children with OA or UCD transplanted between January 2014 and December 2021. Standardized motor and cognitive assessment scores were collected from children who had ≥1 motor/cognitive assessment at any timepoint. Pre-LT brain magnetic resonance imaging (MRI) was graded. Associations between demographic/medical variables and neurodevelopmental outcomes were explored. Twenty-six children (64% male) underwent LT at a median age of 1.4 (interquartile range 0.71, 3.84) years. Fifteen (58%) had a UCD diagnosis, 14 (54%) required dialysis for hyperammonemia, and 10 (42%) had seizures typically around diagnosis. The proportion of children with gross motor scores >1 standard deviation (SD) below the mean increased across timepoints, and ≥50% demonstrated general intellect scores >2 SD below the mean at each timepoint. The following significant associations were noted: UCD diagnoses with lower general intellect scores (p = 0.019); arginosuccinate lyase deficiency diagnosis with lower visual motor scores at 3-years post-LT (p = 0.035); a history of seizures pre-LT with lower general intellect (>2SD below the mean) at 3-years post-LT (p = 0.020); dialysis pre-LT with lower motor scores (>1 SD below the mean) at 1-year post-LT (p = 0.039); pre-emptive LT with higher general intellect scores at 3-years post-LT (p = 0.001). MRI gradings were not associated with developmental scores. In our single centre study, children with UCD or OA had a higher prevalence of developmental impairment post-LT compared to population norms. Earlier screening, pre-emptive transplant, and rehabilitation may optimize long-term outcomes.
本研究描述了尿素循环障碍(UCD)和有机酸血症(OA)患儿在肝移植(LT)前、LT后1年和3年的神经发育结局。我们对2014年1月至2021年12月期间接受移植的OA或UCD患儿进行了回顾性病历审查。从在任何时间点进行了≥1次运动/认知评估的儿童中收集标准化运动和认知评估分数。对LT前的脑磁共振成像(MRI)进行分级。探讨了人口统计学/医学变量与神经发育结局之间的关联。26名儿童(64%为男性)接受了LT,中位年龄为1.4岁(四分位间距0.71,3.84)。15名(58%)诊断为UCD,14名(54%)因高氨血症需要透析,10名(42%)通常在诊断前后出现癫痫发作。粗大运动评分低于平均值>1个标准差(SD)的儿童比例随时间点增加而增加,并且在每个时间点≥50%的儿童表现出一般智力评分低于平均值>2个SD。发现以下显著关联:UCD诊断与较低的一般智力评分相关(p = 0.019);精氨酸琥珀酸裂解酶缺乏症诊断与LT后3年较低的视觉运动评分相关(p = 0.035);LT前有癫痫发作史与LT后3年较低的一般智力(低于平均值>2个SD)相关(p = 0.020);LT前透析与LT后1年较低的运动评分(低于平均值>1个SD)相关(p = 0.039);抢先LT与LT后3年较高的一般智力评分相关(p = 0.001)。MRI分级与发育评分无关。在我们的单中心研究中,与人群标准相比,UCD或OA患儿LT后发育障碍的患病率更高。早期筛查、抢先移植和康复可能会优化长期结局。