Division of Neuropaediatrics and Inherited Metabolic Diseases, Centre for Child and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany.
Division of Metabolism and Children's Research Centre, University Children's Hospital Zurich, Zurich, Switzerland.
J Inherit Metab Dis. 2019 Mar;42(2):243-253. doi: 10.1002/jimd.12013. Epub 2019 Jan 22.
Beginning in 2006, the Urea Cycle Disorders Consortium (UCDC) has conducted a longitudinal study of eight inherited deficiencies of enzymes and transporters of the urea cycle, including 444 individuals with ornithine transcarbamylase deficiency (OTCD), of whom 300 (67 males, 233 females) received psychological evaluation. In a cross-sectional study (age range, 3-71 years), analysis of covariance (ANCOVA) determined the association between outcomes in five cognitive domains (global intelligence, executive functions, memory, visuomotor integration, visual perception) and sex, age at testing and timing of disease onset defined as early onset (≤28 days; EO), late onset (LO), or asymptomatic (AS). The dataset of 183 subjects with complete datasets (31 males, 152 females) revealed underrepresentation of EO subjects (2 males, 4 females), who were excluded from the ANCOVA. Although mean scores of LO and AS individuals were within 1 SD of the population norm, AS subjects attained significantly higher scores than LO subjects and males higher scores than females. Correlations between cognitive domains were high, particularly intelligence proved to be a distinguished indicator for cognitive functioning. Maximum plasma ammonium concentration and intelligence correlated significantly higher in EO (r = -0.47) than in LO subjects (r = 0.04). Correlation between the number of hyperammonemic events and intelligence scores were similar for EO (r = -0.30) and LO (r = -0.26) individuals. The number of clinical symptoms was significantly associated with intelligence (r = -0.28) but not with scores in other domains. Results suggest that OTCD has a global impact on cognitive functioning rather than a specific effect on distinct cognitive domains.
自 2006 年以来，尿素循环障碍联盟（Urea Cycle Disorders Consortium，UCDC）一直对 8 种尿素循环酶和转运蛋白的遗传性缺陷进行纵向研究，其中包括 444 名鸟氨酸转氨甲酰酶缺乏症（ornithine transcarbamylase deficiency，OTCD）患者，其中 300 名（67 名男性，233 名女性）接受了心理评估。在一项横断面研究（年龄范围为 3-71 岁）中，协方差分析（analysis of covariance，ANCOVA）确定了五个认知领域（总体智力、执行功能、记忆、视动整合、视觉感知）的结果与性别、测试时的年龄以及疾病发作时间（定义为早期发作[≤28 天；EO]、晚期发作[LO]或无症状[AS]）之间的关联。183 名具有完整数据集的受试者（31 名男性，152 名女性）的数据集中，EO 受试者（2 名男性，4 名女性）人数不足，他们被排除在 ANCOVA 之外。尽管 LO 和 AS 个体的平均分数在人群正常值的 1 个标准差范围内，但 AS 个体的分数明显高于 LO 个体，男性的分数高于女性。认知领域之间的相关性较高，特别是智力被证明是认知功能的显著指标。EO 组（r=-0.47）的最大血浆氨浓度与智力的相关性明显高于 LO 组（r=0.04）。EO 组（r=-0.30）和 LO 组（r=-0.26）个体的高氨血症事件次数与智力评分的相关性相似。临床症状的数量与智力呈显著相关（r=-0.28），但与其他领域的评分无关。结果表明，OTCD 对认知功能有全面影响，而不是对特定认知领域有特定影响。
